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Thread: Lab Leak: The conspiracy theory is shaping up to look like real possibility

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    Quote Originally Posted by shunyadragon View Post
    The thread has drifted into the name calling mudslinging pig sti.

    Back on topic>

    I watched the video, and it remains hypothetical, and circumstantial evidence does not stand the test of evidence. There is no record of lab personnel getting the virus early, The consumption of the wild animals and the transmission of coronaviruses to humans has a long history. This one just started a pandemic.

    The genetic research publications I presented are based on science, and the conclusions are most likely natural origins. The most likely animal has matching DNA and is sold and consumed in Wuhan via the Wuhan market.

    Statement form the administration:

    Source: https://thehill.com/policy/healthcare/493083-us-officials-investigating-whether-coronavirus-originated-in-chinese




    The theory, which has not yet been corroborated, is reportedly one of multiple possibilities the U.S. is investigating.

    The latest developments come days after the chairman of the Joint Chiefs of Staff, Army Gen. Mark Milley, told reporters that the U.S. intelligence community was taking "a hard look" at the theory.

    "I would just say, at this point, it's inconclusive, although the weight of evidence seems to indicate natural [origin]. But we don't know for certain," he said, referring to the likelihood that the virus originated naturally, rather than in a lab setting.

    © Copyright Original Source

    This was helpful.
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    Quote Originally Posted by shunyadragon View Post
    The thread has drifted into the name calling mudslinging pig sti.

    Back on topic>

    I watched the video, and it remains hypothetical, and circumstantial evidence does not stand the test of evidence. There is no record of lab personnel getting the virus early, The consumption of the wild animals and the transmission of coronaviruses to humans has a long history. This one just started a pandemic.

    The genetic research publications I presented are based on science, and the conclusions are most likely natural origins. The most likely animal has matching DNA and is sold and consumed in Wuhan via the Wuhan market.

    Statement form the administration:

    Source: https://thehill.com/policy/healthcare/493083-us-officials-investigating-whether-coronavirus-originated-in-chinese




    The theory, which has not yet been corroborated, is reportedly one of multiple possibilities the U.S. is investigating.

    The latest developments come days after the chairman of the Joint Chiefs of Staff, Army Gen. Mark Milley, told reporters that the U.S. intelligence community was taking "a hard look" at the theory.

    "I would just say, at this point, it's inconclusive, although the weight of evidence seems to indicate natural [origin]. But we don't know for certain," he said, referring to the likelihood that the virus originated naturally, rather than in a lab setting.

    © Copyright Original Source

    Just out of curiosity, and this is a legit question because I honestly don't know, but has the direct transfer of a virus from a animal (mammal) to a human actually been demonstrated -- like in a controlled research lab under direct observation? And if so, can someone direct me to that study? Every time I come across material about this subject, it always seems to be based on theory.
    Last edited by seanD; 04-18-2020 at 09:02 AM.
    "I was the CIA director. We lied, we cheated, we stole, it was like... we had entire training courses. It reminds you of the glory of the American experiment." - Mike Pompeo, Secretary of State (source).

  3. #213
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    Quote Originally Posted by seanD View Post
    Just out of curiosity, and this is a legit question because I honestly don't know, but has the direct transfer of a virus from a animal (mammal) to a human actually been demonstrated.
    It is common for viruses to migrate from host to host within the animal kingdom including humans naturally. Bird and swine flues are direct transfers from animals to humans naturally.


    [quote] -- like in a controlled research lab under direct observation? And if so, can someone direct me to that study? Every time I come across material about this subject, it
    always seems to be based on theory.
    Yes, lab workers have been contaminated by viruses and got sick before, but this is the same process of transfer anywhere. As far as deliberate transfer in the lab it is possible, but hypothetical with no evidence of this happening at present in the Wuhan lab.
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    [QUOTE=shunyadragon;729806]It is common for viruses to migrate from host to host within the animal kingdom including humans naturally. Bird and swine flues are direct transfers from animals to humans naturally.


    -- like in a controlled research lab under direct observation? And if so, can someone direct me to that study? Every time I come across material about this subject, it

    Yes, lab workers have been contaminated by viruses and got sick before, but this is the same process of transfer anywhere. As far as deliberate transfer in the lab it is possible, but hypothetical with no evidence of this happening at present in the Wuhan lab.
    Can you cite the study where virus cross-species of mammals (from animal to human) was observed? That's what I'm asking.
    "I was the CIA director. We lied, we cheated, we stole, it was like... we had entire training courses. It reminds you of the glory of the American experiment." - Mike Pompeo, Secretary of State (source).

  5. #215
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    Quote Originally Posted by Juvenal View Post
    As easily as I can recognize the dishonesty behind a quote mine. Howzbout you, piglet?
    Not sure what quote mining has to do with the price of tea in ...China here.
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    Quote Originally Posted by simplicio View Post
    Cowpoke truncated the post. It was dishonest. But since CP is a "good" Christian, it is excused.
    Ummmm..... CP properly used the quote function, hyperlink intact, so anybody who wanted to see what was said "in full" can simply click there.
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    Quote Originally Posted by seanD View Post
    Just out of curiosity, and this is a legit question because I honestly don't know, but has the direct transfer of a virus from a animal (mammal) to a human actually been demonstrated -- like in a controlled research lab under direct observation? And if so, can someone direct me to that study? Every time I come across material about this subject, it always seems to be based on theory.
    This is called Zoonosis (article is worth reading) and it's a very common phenomena (~61% of human diseases come from animals).

    It happens frequently to farmers dealing with livestock (even in developed countries) when the animals catch one of the many, many, diseases that are transmissible to humans and which the farmers then themselves catch. The vast majority of the time this happens, that disease is not transmissible from human to human.

    An example of a zoonotic you will be familiar with is Rabies, where a dog or other infected animal, bites a human, and passes Rabies to them by doing so.

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    Quote Originally Posted by seanD View Post
    Can you cite the study where virus cross-species of mammals (from animal to human) was observed? That's what I'm asking.
    I am not sure what you call observed. The closest is they have followed flus in recent history, and found the same genetic match in the animal of origin as found in humans, such as bird and swine flus, and have followed the host to host transfer of the viruses. It is part of the way they develop vaccines. As in China they have developed the closest match as the coronavirus found in the Pangolin. There are other in fact, many different coronaviruses, in the animals and humans, but this is the only close match. This is the same as following viruses in human populations.

    This an example of one of many research on specific transmission:

    Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550509/


    go for it
    Animal models for influenza virus transmission studies: A historical perspective

    Nicole M. Bouvier

    Abstract
    Animal models are used to simulate, under experimental conditions, the complex interactions among host, virus, and environment that affect the person-to-person spread of influenza viruses. The three species that have been most frequently employed, both past and present, as influenza virus transmission models -- ferrets, mice, and guinea pigs -- have each provided unique insights into the factors governing the efficiency with which these viruses pass from an infected host to a susceptible one. This review will highlight a few of these noteworthy discoveries, with a particular focus on the historical contexts in which each model was developed and the advantages and disadvantages of each species with regard to the study of influenza virus transmission among mammals.

    Introduction

    Complex interactions among host, pathogen, and environment determine whether and how well infectious diseases circulate among susceptible populations. To model the human transmission of influenza viruses, many mammalian species -- including mice, Syrian hamsters, guinea pigs, ferrets, domestic swine, and marmosets [1–5] -- have been used elucidate experimental variables that affect the efficiency with which these viruses pass from infected to susceptible host. This review will provide the historical contexts in which the ferret, mouse, and guinea pig models of influenza virus transmission were developed; highlight several critical scientific discoveries made with each model; and discuss the advantages and disadvantages of each species with regard to the study of influenza virus transmission among mammals.

    Go to:
    Ferret modeling of influenza virus transmission: A historical perspective
    Wilson Smith, Christoper H. Andrewes, and Patrick P. Laidlaw first isolated the virus causing human influenza during an epidemic in England in early 1933[6]. In their communication to The Lancet in July of that year, they reported that throat washings from influenza patients had been filtered to remove bacteria, and then the sterile filtrates were “used in attempts to infect many different species” [6]. Wilson Smith’s biographer, D.G. Evans, added further detail to their efforts: “…many different species of animals were being inoculated with the throat garglings from suspected [influenza] cases as well as with lung material from fatal cases. Guinea-pigs, mice, rabbits, hamsters, hedgehogs, and monkeys were used and the routes of inoculation chosen were intracerebral, intratesticular and intraperitoneal. No symptoms developed in any of the species used and Wilson Smith then decided to turn to ferrets,” which were in use in a nearby laboratory to study canine distemper virus [7].

    Smith and colleagues reported that two ferrets were inoculated with throat-washing filtrates “both subcutaneously and by intranasal instillation,” and both subsequently developed an influenza-like illness characterized by “a two-day incubation period, a diphasic temperature response, symptoms of nasal catarrh and variable systemic disturbances…. Coincidently with the primary rise of temperature the ferret looks ill, is quiet and lethargic, often refuses food, and may show signs of muscular weakness. The catarrhal symptoms usually begin on the third day. The eyes become watery and there is a variable amount of watery discharge from the nose…. The animal sneezes frequently, yawns repeatedly, and in many cases breathes partly through the mouth with wheezy or stertorous sounds…. The signs of illness may last for only a few days but sometimes continue for ten days, after which the ferret again becomes perfectly normal” [6].

    Thus, the first successful isolation of a human influenza virus ultimately depended upon several fortuitous experimental choices, particularly the use of a biologically relevant route of inoculation in an animal species that was susceptible to productive infection with human influenza virus and that showed signs of disease resembling the human illness [7].

    By the time of their 1933 publication in The Lancet, Smith and colleagues had already observed that the virus they had isolated could spread from ferret to ferret: “The disease has frequently been transmitted by placing a normal ferret in the same cage as a sick one for 24 hours” [6]. Interspecies transmission was hypothesized when Wilson Smith came down with influenza in March 1933; “it was suspected that he had caught it from a ferret” [7]. While ill, Smith inoculated his own filtered throat washings back into a naïve ferret, thus originating the “WS” strain [7]. Its descendant, the neurotropic mouse-adapted strain A/WSN/1933 (“WSN,” an acronym for “Wilson Smith Neurotropic”) [8], is still in common use in influenza virology laboratories worldwide.

    Initially, the only known way to maintain and propagate influenza viruses was to passage them from ferret to ferret. In fact, the first influenza virus isolate -- the one described in The Lancet in 1933 -- was ultimately lost when the influenza ferret colony perished in an outbreak of canine distemper [7]. Thus, the ferret model has been associated with influenza virology, and influenza virus transmissibility, from the field’s very beginning.

    Go to:
    Ferret modeling of influenza virus transmission: Key discoveries
    In 1934, at the Rockefeller Institute in New York City, Thomas Francis Jr. successfully replicated the ferret experiments of Smith and colleagues. In Science, he reported that three glycerine-preserved sputum samples, collected during an influenza epidemic in Puerto Rico in the late summer and fall of 1934, could induce influenza disease in inoculated ferrets. Francis also remarked that, “in the course of the experimental work with ferrets,” a laboratory assistant fell ill with influenza. Nasopharyngeal washings from the laboratory assistant, inoculated back into a healthy, naïve ferret, produced influenza-like illness [9]. The virus isolate with which these experiments were performed, called “P.R. 5” in Francis’ report, was subsequently lost. However, a contemporaneously isolated virus from the 1934 Puerto Rico epidemic, which Francis called “P.R. 8” [10], still survives, propagated and passed on from lab to lab by generations of influenza virologists. Designated A/Puerto Rico/8/1934(H1N1) in contemporary influenza virus nomenclature, PR8 has become the prototypical laboratory strain of influenza A virus.

    In the early spring of 1940, Francis obtained throat washings from “Lee,” a child with influenza-like illness. Inoculation of a ferret with this specimen produced mild clinical signs and pathology compared to the WS or PR8 strains, including hypothermia, anorexia, lethargy, respiratory distress, and, upon necropsy on day 6 post-inoculation, only a “mild bluish discoloration of the left lower lobe of the lung.” Serum samples from patients who had had typical influenza-like illness during the winter of 1940 failed to show appreciable antibody titers against PR8, but most had high antibody reactivity to the Lee virus. “It is evident, therefore,” wrote Francis in Science [11], “that … the Lee virus represents a serologically distinct entity. Nevertheless, the epidemic disease associated with virus of the Lee type appears … to be as typical of epidemic influenza as that … from which strains of the previously recognized virus were obtained.” However, he perceptively observed, “the two infections apparently possess independent cycles” of epidemic circulation. Francis suggested that influenza viruses serologically related to PR8, WS, and others like them be called “Influenza A,” and those related to the Lee strain be designated “Influenza B.” Subsequently mouse-adapted, B/Lee/1940 remains in use in influenza labs today.

    Not long thereafter, in 1941, C. H. Andrewes and R.E. Glover published an influential paper describing the modes of transmission of influenza A viruses among ferrets [12]. Influenza and other respiratory viruses are thought to spread from person to person by contact and airborne routes [13, 14]. Direct contact transmission is characterized by the transfer of viable virus from an infected person directly onto a susceptible person’s hand. In indirect contact transmission, infectious virus is conveyed onto the hand of a susceptible person by touching an inanimate object that has been contaminated by an infectious person. In both contact modes, though, the susceptible person introduces the virus into his or her own respiratory tract by transferring it from hand to respiratory mucosa. In contrast, in airborne transmission, inoculation of the susceptible person’s respiratory tract occurs directly from the air, without a hand or other intermediate object that introduces virus into the respiratory tract. In droplet spray transmission, an infected person expels virus-laden respiratory droplets by coughing or sneezing; these infectious droplets then impact directly on the respiratory mucosa of a susceptible person. Aerosol transmission occurs when infectious respiratory droplets exhaled or expelled by an infectious person partially desiccate before settling to ground. These aerosols -- also called droplet nuclei -- are small and light, remaining suspended in the air for minutes to hours. Some aerosols dry out too much, so that the virus is rendered non-viable, while others are removed from the air by ventilation or gravity. However, some aerosols may be inhaled into the respiratory tract of a susceptible person and initiate infection [14].

    Andrewes and Glover confirmed that influenza virus is passed readily between infected and susceptible ferrets in the same cage, but these experiments could not determine whether transmission was occurring by contact or airborne routes; with co-caged animals, all modes of transmission are theoretically possible. When individual ferrets were placed into solid metal cages placed side-by-side, transmission from infected to susceptible animal was rare; however, if open wire-mesh cages were used instead, virus transmission could occur between ferrets caged up to 1.5 m (5 feet) apart, even when the susceptible ferret was placed higher above the ground than the infected one. When windows in the animal room were opened to increase ventilation, though, ferret-to-ferret transmission was abolished. Although these results suggested aerosol transmission, Andrewes and Glover designed an elegant series of experiments to confirm it. They constructed several wooden ducts through which air was pulled slowly at 7 cm/s (14 ft./min.) by an exhaust fan at one end. When an infected ferret was placed at the air-intake end of the duct and a susceptible ferret at the air-exhaust end, influenza virus transmission occurred through a U-shaped duct, 3 m (10 feet) in length from end to end, a result most consistent with infectious airborne virus carried through the duct in or on aerosol-sized particles [12].

    Although evidence suggests that aerosols can initiate influenza virus infections in both ferrets and humans [15, 16], the relative importance of airborne and contact transmission remains unknown in either species. The airborne transmission model, however, is often used to estimate the pandemic potential of emerging non-human or novel human influenza viruses [17]. Airborne transmissibility among ferrets has generally correlated with transmissibility among humans. For example, the swine-origin influenza A(H1N1) virus that caused the 2009 pandemic was also highly transmissible among ferrets [18–20], while ferret transmissibility is less efficient for influenza viruses that sporadically infect humans from the avian [21–27] or swine [28, 29] reservoirs but do not demonstrate sustained person-to-person spread.

    Novel, emerging influenza viruses, such as those noted above, often attract much scientific and public attention and are thus evaluated in the ferret model by several different research groups. In that case, collectively assessing the data from many different experiments may make it possible to draw general conclusions about the ferret transmissibility of individual viruses or strains [30]. However, individual ferret experiments are often underpowered to achieve statistically significant results [31, 32]. Ferrets require more intensive animal husbandry than smaller animals; thus, the main drawback of the ferret model is their relative cost, not only for purchase and maintenance expenses but also for the physical space required to house them.

    Though highly pathogenic avian influenza (HPAI) H5N1 viruses have demonstrated poor ferret transmissibility [22, 25], two controversial manuscripts, published in 2012, detailed the creation of ferret-transmissible influenza A viruses expressing the highly pathogenic avian influenza (HPAI) H5 hemagglutinin (HA) to which most humans are immunologically naïve [33, 34]. A public debate erupted over the publication of this “dual-use research of concern” (DURC) [35, 36], “life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat … to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security” [37]. The specific amino acid mutations that rendered the H5 viruses ferret-transmissible were not identical in the two studies; however, the effects of the individual mutations upon HA activity were similar [38]. Thus, these studies highlighted functional adaptations that appeared to be necessary for efficient mammalian transmission of H5 viruses in general, leading some to suggest that publishing the manuscripts posed a biosecurity risk [39]. To allow for public and scientific discussion and deliberation, influenza transmission researchers self-imposed a 60-day moratorium on performing similar experiments [40], which extended to a year [41]. However, reverberations from the implications of these two studies continue to be felt. In October 2014, the U.S. Government announced that it would withhold new federal funding while deliberating the risks and benefits of “gain-of-function” research -- that which “may be reasonably anticipated to confer attributes to influenza … viruses such that the virus would have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route” [42], effectively halting for the time being such research in the United States.

    Go to:
    Mouse modeling of influenza virus transmission: A historical perspective
    Thomas Francis’ “P.R. 5” and “P.R. 8” viruses, isolated in ferrets in 1934, were initially poorly infectious in mice; however, serial passaging in mice enhanced their murine infectivity and pathogenicity. Since then, mice have provided a low-cost, convenient, small-animal alternative to the ferret model for studying influenza disease. However, prior mouse adaptation of human influenza virus isolates is required for productive infection, limiting the strains available for murine experiments.

    Attempts to establish a mouse model for influenza virus transmission have been relatively less successful. In 1940, Monroe D. Eaton reported on transmission experiments that he had performed with the mouse-adapted lab strains WS and PR8 [43]. In these experiments, mice that had been intranasally inoculated an influenza virus were co-housed with uninfected contact mice. Eaton observed that infection in inoculated mice was nearly always fatal, but the contact mice rarely succumbed to disease. However, upon necropsy, contact mice often demonstrated lung consolidations characteristic of influenza pneumonia, suggesting that influenza virus had transmitted to them from the inoculated mice. Eaton reported highly efficient transmission in this model, with up to 88% or 100% of contact mice (for PR8 and WS, respectively) displaying the typical lung pathology of influenza [43].

    For over 20 years, however, other researchers were unable to replicate the efficient transmission observed by Eaton [44]. Finally, in the 1960s, Schulman and Kilbourne succeeded in establishing a murine transmission model with influenza A(H2N2) viruses, which began circulating among humans during the 1957 “Asian flu” pandemic. Schulman tested influenza virus transmission between infected and susceptible mice in the same cage, as Eaton had done, and also when infected and susceptible mice were physically separated by a 3/4-inch (1.9 cm) thick, air-permeable, wire-mesh divider [44, 45]. Transmission events could only be confirmed by necropsy of the contact mice, similar to Eaton’s method; Schulman, however, subsequently inoculated homogenates from the lungs of contact mice into embryonated hen’s eggs to confirm that viable influenza virus was present [44]. Contrary to Eaton’s report, Schulman observed poor transmissibility of PR8 and WSN, with transmission occurring less than 10% of the time among his mice [46, 47]. However, many influenza A(H2N2) isolates transmitted among mice with relative efficiency, such as the mouse-adapted pandemic strain A/Japan/305/1957 (62.5% transmission rate) [47].

    Go to:
    Mouse modeling of influenza virus transmission: Key discoveries
    Despite the inconsistencies in the efficiency of murine transmissibility of influenza viruses, Schulman was able to replicate some of Eaton’s earlier findings. Both reported that transmission efficiency was maximal when infected and contact mice were together between 24 and 48 hours post-inoculation of the infected mice [43, 44] and that older mice were more susceptible to transmitted infection than younger mice [43, 48]. In addition, Schulman made some prescient discoveries about influenza virus transmission that have since been observed in other animal models. He found that airflow and humidity affected airborne influenza virus transmission among mice, with rapid airflow and high humidity decreasing transmission efficiency [45]; that transmission efficiency was higher in the winter than in the summer, even when transmission experiments were conducted in temperature- and humidity-controlled environments [48]; and that a virus strain that transmitted well among his mice could be sampled from the air surrounding infected mice at higher titers than could a virus that transmitted poorly, even though the two strains demonstrated identical lung titers [46]. Similar findings in the guinea pig model [49–52], discussed in the next section of this review, suggest that certain variables governing the efficiency of influenza virus transmission, at least among rodents if not among all mammals, may be independent of the model used.

    In a more recent evaluation of the murine transmissibility of five influenza A viruses -- including the mouse-adapted laboratory strain WSN; two human seasonal influenza A/H1N1 and A/H3N2 isolates; a highly pathogenic avian A/H5N1 virus; and the reconstructed 1918 pandemic influenza A strain -- none of the viruses were detected in respiratory tissues of BALB/c contact mice, and none of the contact mice seroconverted [50]. These results, along with those of Eaton and Schulman, suggest that murine transmission of influenza viruses is inconsistently efficient, most likely limited by ill-defined factors such as the strain of mouse or virus used, and perhaps by specific experimental set-ups that are difficult to replicate in other laboratories.

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    Guinea pig modeling of influenza virus transmission: A historical perspective
    Though the guinea pig is a frequently employed and well-characterized model for non-infectious respiratory diseases like asthma and chronic obstructive pulmonary disease [53] and for the bacterial respiratory diseases tuberculosis [54] and legionellosis [55], their use in viral respiratory disease had, until recently, been mainly limited to paramyxoviruses such as parainfluenzavirus and respiratory syncytial virus (RSV) [56–59].

    Influenza virus pathogenesis had occasionally been studied in guinea pigs [60–64]; however, in 2006, the development of the guinea pig model of influenza virus transmission in the lab of Peter Palese [50] opened up new avenues of investigation. While reviewing primary medical literature describing the impact of the 1918 “Spanish” influenza pandemic, Palese came across an account, published in JAMA in 1919, that described the influenza outbreak that occurred in the fall of 1918 at Camp Cody, a World War I Army camp near Deming, New Mexico. In addition to describing the pathophysiology, epidemiology, and microbiology of pandemic influenza among the camp’s soldiers and personnel, the physician authors wrote, “it is interesting to note that very soon after the epidemic of influenza reached this camp our laboratory guinea-pigs, housed in a small building beside the laboratory, began to die” [65]. The authors observed, “The guinea-pigs were sick from two to four days before death. During this time, the sick animal trembling from chills, with hair ruffled, sat huddled up in a corner of the pen … until shortly before death. The respirations were rapid and wheezing; the characteristic shrill whistle became scarcely audible. The animal was apparently in a stupor which gradually deepened until death supervened” [65].

    The influenza epidemic appeared to spread rapidly through the camp’s guinea pig colony, just as it had among Camp Cody’s human population: “All of the [guinea] pigs in a batch of thirty died within three weeks. Fifty more were received from El Paso, Texas, … apparently healthy…. No deaths occurred for about two weeks. One morning one pig was found dead, and within three weeks all of this second group had died just as the first had done. Segregating the sick animals did not save the others.” The authors commented, “…this epidemic among the animals … was so strikingly similar to the influenza epidemic in man” [65].

    Given the apparent spread of 1918 pandemic influenza virus among guinea pigs in the Camp Cody colony, Palese wondered whether the species might, like ferrets, be a model for studying influenza virus transmission (P Palese, personal communication). His laboratory went on to demonstrate that commercially available, outbred Hartley strain guinea pigs could be productively infected with an unadapted human isolate by intranasal inoculation and could transmit the virus both to uninfected cage-mates and to naïve guinea pigs in cages up to 91 cm (3 feet) away [50]. Inbred Strain 2 and Strain 13 guinea pigs were similarly susceptible to infection with human influenza virus strains and could transmit virus to susceptible partner animals; however, inbred colonies are privately held and are less readily procured than are commercially bred Hartley guinea pigs [50, 52, 66]. Further research by the Palese group has demonstrated the presence of antibodies to human influenza viruses in livestock guinea pigs raised in three different regions of Ecuador, where guinea pig meat (cuy) is part of the traditional Andean cuisine [67]. Although influenza viruses seem not to be enzootic in guinea pigs, they do appear capable of jumping the species barrier from infected human farmers into their livestock guinea pigs and may also circulate among guinea pig herds under non-experimental conditions. However, influenza virus spread among guinea pigs outside of the lab has yet to be documented, likely because the absence of clinical signs of infection makes identifying influenza outbreaks in livestock herds more challenging [67].

    Thus, the main disadvantage of the guinea pig model is that, unlike ferrets, guinea pigs show minimal clinical evidence of influenza virus infection [2, 68, 69], even remaining overtly unaffected by infection with HPAI strains that are fatal to mice and ferrets [70, 71]. Further research is needed to understand the role of symptomatology in influenza virus transmission in both animal models and in humans, in whom subclinical infection and asymptomatic virus shedding may be underappreciated [72, 73].

    Go to:
    Guinea pig modeling of influenza virus transmission: Key discoveries
    Complementing Schulman’s finding that rapid airflow speed decreases influenza virus transmission among mice, a few observations regarding airflow have been made in the guinea pig model. In their initial guinea pig transmission experiments, the Palese group noted that influenza virus transmission could occur over distances up to 91 cm, but that “…transmission was not observed when the relative positions of the infected and uninfected animals were reversed, suggesting that spread depended on the direction of airflow in the room” [50]. Subsequent experiments, performed in environmentally controlled chambers with an upward directional airflow, demonstrated influenza virus transmission when uninfected guinea pigs were placed 100 cm above infected animals, against gravity but with the chambers’ intrinsic airflow [52].

    The Palese group also studied the effects of relative humidity (RH) and temperature on influenza virus transmission in the environmentally controlled chambers. At various combinations of temperature (5, 20, or 30°C) and RH (20, 35, 50, 65, and 80%), the transmission efficiency of A/Panama/2007/1999(H3N2) increased as temperature decreased, with a similar general trend towards increased transmission efficiency was observed with decreasing humidity [49, 51, 74], similar to that observed by Schulman in the mouse model [45]. The same inverse correlation between transmission efficiency and ambient temperature has since been demonstrated in influenza A(H1N1), A(H1N1pdm09), and influenza B viruses [74–76]. Of note, guinea pigs can transmit influenza B viruses, which has yet to be demonstrated in ferrets [76].

    Go to:
    Concluding remarks
    Many mammalian animal models have been used in influenza virus transmission research, including cotton rats, Syrian hamsters, cats, dogs, domestic pigs, and non-human primates. In this review, we have discussed ferrets, mice, and guinea pigs, the three models used most frequently in the past and currently.

    Like humans, seasonal influenza in the ferret is manifested by fever, nasal discharge, lethargy, anorexia, and sneezing, while infection with HPAI viruses can result in severe disease and death. Because influenza is not clinically apparent in guinea pigs, they cannot be used to study interventions designed to reduce morbidity or mortality. However, both models are readily susceptible to infection with human influenza virus isolates, demonstrating robust viral replication and efficient transmission of virus to others of their species. In contrast, human influenza viruses are poorly infectious in mice, requiring the use of previously mouse-adapted strains. Even after adaptation, though, inconsistent results have been obtained when assessing the transmissibility of mouse-infecting strains such as PR8, WSN, and A/Japan/305/1957.

    The main drawback to the ferret as a model for influenza virus transmission is its cost, due to its relatively lower commercial availability, larger size, and more complex husbandry requirements, and adequately powered experiments can be costly to achieve. Statistically robust data can, however, be obtained at less expense in rodent models.

    Thus, there are a variety of animal models in which to study the transmission of influenza viruses, each with advantages and disadvantages that must be understood and considered when designing and performing influenza virus transmission experiments in animal models.

    © Copyright Original Source



    Last edited by shunyadragon; 04-18-2020 at 02:39 PM.
    Glendower: I can call spirits from the vasty deep.
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  9. #219
    tWebber EvoUK's Avatar
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    Quote Originally Posted by shunyadragon View Post
    I am not sure what you call observed. The closest is they have followed flus in recent history, and found the same genetic match in the animal of origin as found in humans, such as bird and swine flus, and have followed the host to host transfer of the viruses. It is part of the way they develop vaccines. As in China they have developed the closest match as the coronavirus found in the Pangolin. There are other in fact, many different coronaviruses, in the animals and humans, but this is the only close match. This is the same as following viruses in human populations.

    This an example of one of many research on specific transmission:

    Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550509/


    go for it
    Animal models for influenza virus transmission studies: A historical perspective

    Nicole M. Bouvier

    Abstract
    Animal models are used to simulate, under experimental conditions, the complex interactions among host, virus, and environment that affect the person-to-person spread of influenza viruses. The three species that have been most frequently employed, both past and present, as influenza virus transmission models -- ferrets, mice, and guinea pigs -- have each provided unique insights into the factors governing the efficiency with which these viruses pass from an infected host to a susceptible one. This review will highlight a few of these noteworthy discoveries, with a particular focus on the historical contexts in which each model was developed and the advantages and disadvantages of each species with regard to the study of influenza virus transmission among mammals.

    Introduction

    Complex interactions among host, pathogen, and environment determine whether and how well infectious diseases circulate among susceptible populations. To model the human transmission of influenza viruses, many mammalian species -- including mice, Syrian hamsters, guinea pigs, ferrets, domestic swine, and marmosets [1–5] -- have been used elucidate experimental variables that affect the efficiency with which these viruses pass from infected to susceptible host. This review will provide the historical contexts in which the ferret, mouse, and guinea pig models of influenza virus transmission were developed; highlight several critical scientific discoveries made with each model; and discuss the advantages and disadvantages of each species with regard to the study of influenza virus transmission among mammals.

    Go to:
    Ferret modeling of influenza virus transmission: A historical perspective
    Wilson Smith, Christoper H. Andrewes, and Patrick P. Laidlaw first isolated the virus causing human influenza during an epidemic in England in early 1933[6]. In their communication to The Lancet in July of that year, they reported that throat washings from influenza patients had been filtered to remove bacteria, and then the sterile filtrates were “used in attempts to infect many different species” [6]. Wilson Smith’s biographer, D.G. Evans, added further detail to their efforts: “…many different species of animals were being inoculated with the throat garglings from suspected [influenza] cases as well as with lung material from fatal cases. Guinea-pigs, mice, rabbits, hamsters, hedgehogs, and monkeys were used and the routes of inoculation chosen were intracerebral, intratesticular and intraperitoneal. No symptoms developed in any of the species used and Wilson Smith then decided to turn to ferrets,” which were in use in a nearby laboratory to study canine distemper virus [7].

    Smith and colleagues reported that two ferrets were inoculated with throat-washing filtrates “both subcutaneously and by intranasal instillation,” and both subsequently developed an influenza-like illness characterized by “a two-day incubation period, a diphasic temperature response, symptoms of nasal catarrh and variable systemic disturbances…. Coincidently with the primary rise of temperature the ferret looks ill, is quiet and lethargic, often refuses food, and may show signs of muscular weakness. The catarrhal symptoms usually begin on the third day. The eyes become watery and there is a variable amount of watery discharge from the nose…. The animal sneezes frequently, yawns repeatedly, and in many cases breathes partly through the mouth with wheezy or stertorous sounds…. The signs of illness may last for only a few days but sometimes continue for ten days, after which the ferret again becomes perfectly normal” [6].

    Thus, the first successful isolation of a human influenza virus ultimately depended upon several fortuitous experimental choices, particularly the use of a biologically relevant route of inoculation in an animal species that was susceptible to productive infection with human influenza virus and that showed signs of disease resembling the human illness [7].

    By the time of their 1933 publication in The Lancet, Smith and colleagues had already observed that the virus they had isolated could spread from ferret to ferret: “The disease has frequently been transmitted by placing a normal ferret in the same cage as a sick one for 24 hours” [6]. Interspecies transmission was hypothesized when Wilson Smith came down with influenza in March 1933; “it was suspected that he had caught it from a ferret” [7]. While ill, Smith inoculated his own filtered throat washings back into a naïve ferret, thus originating the “WS” strain [7]. Its descendant, the neurotropic mouse-adapted strain A/WSN/1933 (“WSN,” an acronym for “Wilson Smith Neurotropic”) [8], is still in common use in influenza virology laboratories worldwide.

    Initially, the only known way to maintain and propagate influenza viruses was to passage them from ferret to ferret. In fact, the first influenza virus isolate -- the one described in The Lancet in 1933 -- was ultimately lost when the influenza ferret colony perished in an outbreak of canine distemper [7]. Thus, the ferret model has been associated with influenza virology, and influenza virus transmissibility, from the field’s very beginning.

    Go to:
    Ferret modeling of influenza virus transmission: Key discoveries
    In 1934, at the Rockefeller Institute in New York City, Thomas Francis Jr. successfully replicated the ferret experiments of Smith and colleagues. In Science, he reported that three glycerine-preserved sputum samples, collected during an influenza epidemic in Puerto Rico in the late summer and fall of 1934, could induce influenza disease in inoculated ferrets. Francis also remarked that, “in the course of the experimental work with ferrets,” a laboratory assistant fell ill with influenza. Nasopharyngeal washings from the laboratory assistant, inoculated back into a healthy, naïve ferret, produced influenza-like illness [9]. The virus isolate with which these experiments were performed, called “P.R. 5” in Francis’ report, was subsequently lost. However, a contemporaneously isolated virus from the 1934 Puerto Rico epidemic, which Francis called “P.R. 8” [10], still survives, propagated and passed on from lab to lab by generations of influenza virologists. Designated A/Puerto Rico/8/1934(H1N1) in contemporary influenza virus nomenclature, PR8 has become the prototypical laboratory strain of influenza A virus.

    In the early spring of 1940, Francis obtained throat washings from “Lee,” a child with influenza-like illness. Inoculation of a ferret with this specimen produced mild clinical signs and pathology compared to the WS or PR8 strains, including hypothermia, anorexia, lethargy, respiratory distress, and, upon necropsy on day 6 post-inoculation, only a “mild bluish discoloration of the left lower lobe of the lung.” Serum samples from patients who had had typical influenza-like illness during the winter of 1940 failed to show appreciable antibody titers against PR8, but most had high antibody reactivity to the Lee virus. “It is evident, therefore,” wrote Francis in Science [11], “that … the Lee virus represents a serologically distinct entity. Nevertheless, the epidemic disease associated with virus of the Lee type appears … to be as typical of epidemic influenza as that … from which strains of the previously recognized virus were obtained.” However, he perceptively observed, “the two infections apparently possess independent cycles” of epidemic circulation. Francis suggested that influenza viruses serologically related to PR8, WS, and others like them be called “Influenza A,” and those related to the Lee strain be designated “Influenza B.” Subsequently mouse-adapted, B/Lee/1940 remains in use in influenza labs today.

    Not long thereafter, in 1941, C. H. Andrewes and R.E. Glover published an influential paper describing the modes of transmission of influenza A viruses among ferrets [12]. Influenza and other respiratory viruses are thought to spread from person to person by contact and airborne routes [13, 14]. Direct contact transmission is characterized by the transfer of viable virus from an infected person directly onto a susceptible person’s hand. In indirect contact transmission, infectious virus is conveyed onto the hand of a susceptible person by touching an inanimate object that has been contaminated by an infectious person. In both contact modes, though, the susceptible person introduces the virus into his or her own respiratory tract by transferring it from hand to respiratory mucosa. In contrast, in airborne transmission, inoculation of the susceptible person’s respiratory tract occurs directly from the air, without a hand or other intermediate object that introduces virus into the respiratory tract. In droplet spray transmission, an infected person expels virus-laden respiratory droplets by coughing or sneezing; these infectious droplets then impact directly on the respiratory mucosa of a susceptible person. Aerosol transmission occurs when infectious respiratory droplets exhaled or expelled by an infectious person partially desiccate before settling to ground. These aerosols -- also called droplet nuclei -- are small and light, remaining suspended in the air for minutes to hours. Some aerosols dry out too much, so that the virus is rendered non-viable, while others are removed from the air by ventilation or gravity. However, some aerosols may be inhaled into the respiratory tract of a susceptible person and initiate infection [14].

    Andrewes and Glover confirmed that influenza virus is passed readily between infected and susceptible ferrets in the same cage, but these experiments could not determine whether transmission was occurring by contact or airborne routes; with co-caged animals, all modes of transmission are theoretically possible. When individual ferrets were placed into solid metal cages placed side-by-side, transmission from infected to susceptible animal was rare; however, if open wire-mesh cages were used instead, virus transmission could occur between ferrets caged up to 1.5 m (5 feet) apart, even when the susceptible ferret was placed higher above the ground than the infected one. When windows in the animal room were opened to increase ventilation, though, ferret-to-ferret transmission was abolished. Although these results suggested aerosol transmission, Andrewes and Glover designed an elegant series of experiments to confirm it. They constructed several wooden ducts through which air was pulled slowly at 7 cm/s (14 ft./min.) by an exhaust fan at one end. When an infected ferret was placed at the air-intake end of the duct and a susceptible ferret at the air-exhaust end, influenza virus transmission occurred through a U-shaped duct, 3 m (10 feet) in length from end to end, a result most consistent with infectious airborne virus carried through the duct in or on aerosol-sized particles [12].

    Although evidence suggests that aerosols can initiate influenza virus infections in both ferrets and humans [15, 16], the relative importance of airborne and contact transmission remains unknown in either species. The airborne transmission model, however, is often used to estimate the pandemic potential of emerging non-human or novel human influenza viruses [17]. Airborne transmissibility among ferrets has generally correlated with transmissibility among humans. For example, the swine-origin influenza A(H1N1) virus that caused the 2009 pandemic was also highly transmissible among ferrets [18–20], while ferret transmissibility is less efficient for influenza viruses that sporadically infect humans from the avian [21–27] or swine [28, 29] reservoirs but do not demonstrate sustained person-to-person spread.

    Novel, emerging influenza viruses, such as those noted above, often attract much scientific and public attention and are thus evaluated in the ferret model by several different research groups. In that case, collectively assessing the data from many different experiments may make it possible to draw general conclusions about the ferret transmissibility of individual viruses or strains [30]. However, individual ferret experiments are often underpowered to achieve statistically significant results [31, 32]. Ferrets require more intensive animal husbandry than smaller animals; thus, the main drawback of the ferret model is their relative cost, not only for purchase and maintenance expenses but also for the physical space required to house them.

    Though highly pathogenic avian influenza (HPAI) H5N1 viruses have demonstrated poor ferret transmissibility [22, 25], two controversial manuscripts, published in 2012, detailed the creation of ferret-transmissible influenza A viruses expressing the highly pathogenic avian influenza (HPAI) H5 hemagglutinin (HA) to which most humans are immunologically naïve [33, 34]. A public debate erupted over the publication of this “dual-use research of concern” (DURC) [35, 36], “life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat … to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security” [37]. The specific amino acid mutations that rendered the H5 viruses ferret-transmissible were not identical in the two studies; however, the effects of the individual mutations upon HA activity were similar [38]. Thus, these studies highlighted functional adaptations that appeared to be necessary for efficient mammalian transmission of H5 viruses in general, leading some to suggest that publishing the manuscripts posed a biosecurity risk [39]. To allow for public and scientific discussion and deliberation, influenza transmission researchers self-imposed a 60-day moratorium on performing similar experiments [40], which extended to a year [41]. However, reverberations from the implications of these two studies continue to be felt. In October 2014, the U.S. Government announced that it would withhold new federal funding while deliberating the risks and benefits of “gain-of-function” research -- that which “may be reasonably anticipated to confer attributes to influenza … viruses such that the virus would have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route” [42], effectively halting for the time being such research in the United States.

    Go to:
    Mouse modeling of influenza virus transmission: A historical perspective
    Thomas Francis’ “P.R. 5” and “P.R. 8” viruses, isolated in ferrets in 1934, were initially poorly infectious in mice; however, serial passaging in mice enhanced their murine infectivity and pathogenicity. Since then, mice have provided a low-cost, convenient, small-animal alternative to the ferret model for studying influenza disease. However, prior mouse adaptation of human influenza virus isolates is required for productive infection, limiting the strains available for murine experiments.

    Attempts to establish a mouse model for influenza virus transmission have been relatively less successful. In 1940, Monroe D. Eaton reported on transmission experiments that he had performed with the mouse-adapted lab strains WS and PR8 [43]. In these experiments, mice that had been intranasally inoculated an influenza virus were co-housed with uninfected contact mice. Eaton observed that infection in inoculated mice was nearly always fatal, but the contact mice rarely succumbed to disease. However, upon necropsy, contact mice often demonstrated lung consolidations characteristic of influenza pneumonia, suggesting that influenza virus had transmitted to them from the inoculated mice. Eaton reported highly efficient transmission in this model, with up to 88% or 100% of contact mice (for PR8 and WS, respectively) displaying the typical lung pathology of influenza [43].

    For over 20 years, however, other researchers were unable to replicate the efficient transmission observed by Eaton [44]. Finally, in the 1960s, Schulman and Kilbourne succeeded in establishing a murine transmission model with influenza A(H2N2) viruses, which began circulating among humans during the 1957 “Asian flu” pandemic. Schulman tested influenza virus transmission between infected and susceptible mice in the same cage, as Eaton had done, and also when infected and susceptible mice were physically separated by a 3/4-inch (1.9 cm) thick, air-permeable, wire-mesh divider [44, 45]. Transmission events could only be confirmed by necropsy of the contact mice, similar to Eaton’s method; Schulman, however, subsequently inoculated homogenates from the lungs of contact mice into embryonated hen’s eggs to confirm that viable influenza virus was present [44]. Contrary to Eaton’s report, Schulman observed poor transmissibility of PR8 and WSN, with transmission occurring less than 10% of the time among his mice [46, 47]. However, many influenza A(H2N2) isolates transmitted among mice with relative efficiency, such as the mouse-adapted pandemic strain A/Japan/305/1957 (62.5% transmission rate) [47].

    Go to:
    Mouse modeling of influenza virus transmission: Key discoveries
    Despite the inconsistencies in the efficiency of murine transmissibility of influenza viruses, Schulman was able to replicate some of Eaton’s earlier findings. Both reported that transmission efficiency was maximal when infected and contact mice were together between 24 and 48 hours post-inoculation of the infected mice [43, 44] and that older mice were more susceptible to transmitted infection than younger mice [43, 48]. In addition, Schulman made some prescient discoveries about influenza virus transmission that have since been observed in other animal models. He found that airflow and humidity affected airborne influenza virus transmission among mice, with rapid airflow and high humidity decreasing transmission efficiency [45]; that transmission efficiency was higher in the winter than in the summer, even when transmission experiments were conducted in temperature- and humidity-controlled environments [48]; and that a virus strain that transmitted well among his mice could be sampled from the air surrounding infected mice at higher titers than could a virus that transmitted poorly, even though the two strains demonstrated identical lung titers [46]. Similar findings in the guinea pig model [49–52], discussed in the next section of this review, suggest that certain variables governing the efficiency of influenza virus transmission, at least among rodents if not among all mammals, may be independent of the model used.

    In a more recent evaluation of the murine transmissibility of five influenza A viruses -- including the mouse-adapted laboratory strain WSN; two human seasonal influenza A/H1N1 and A/H3N2 isolates; a highly pathogenic avian A/H5N1 virus; and the reconstructed 1918 pandemic influenza A strain -- none of the viruses were detected in respiratory tissues of BALB/c contact mice, and none of the contact mice seroconverted [50]. These results, along with those of Eaton and Schulman, suggest that murine transmission of influenza viruses is inconsistently efficient, most likely limited by ill-defined factors such as the strain of mouse or virus used, and perhaps by specific experimental set-ups that are difficult to replicate in other laboratories.

    Go to:
    Guinea pig modeling of influenza virus transmission: A historical perspective
    Though the guinea pig is a frequently employed and well-characterized model for non-infectious respiratory diseases like asthma and chronic obstructive pulmonary disease [53] and for the bacterial respiratory diseases tuberculosis [54] and legionellosis [55], their use in viral respiratory disease had, until recently, been mainly limited to paramyxoviruses such as parainfluenzavirus and respiratory syncytial virus (RSV) [56–59].

    Influenza virus pathogenesis had occasionally been studied in guinea pigs [60–64]; however, in 2006, the development of the guinea pig model of influenza virus transmission in the lab of Peter Palese [50] opened up new avenues of investigation. While reviewing primary medical literature describing the impact of the 1918 “Spanish” influenza pandemic, Palese came across an account, published in JAMA in 1919, that described the influenza outbreak that occurred in the fall of 1918 at Camp Cody, a World War I Army camp near Deming, New Mexico. In addition to describing the pathophysiology, epidemiology, and microbiology of pandemic influenza among the camp’s soldiers and personnel, the physician authors wrote, “it is interesting to note that very soon after the epidemic of influenza reached this camp our laboratory guinea-pigs, housed in a small building beside the laboratory, began to die” [65]. The authors observed, “The guinea-pigs were sick from two to four days before death. During this time, the sick animal trembling from chills, with hair ruffled, sat huddled up in a corner of the pen … until shortly before death. The respirations were rapid and wheezing; the characteristic shrill whistle became scarcely audible. The animal was apparently in a stupor which gradually deepened until death supervened” [65].

    The influenza epidemic appeared to spread rapidly through the camp’s guinea pig colony, just as it had among Camp Cody’s human population: “All of the [guinea] pigs in a batch of thirty died within three weeks. Fifty more were received from El Paso, Texas, … apparently healthy…. No deaths occurred for about two weeks. One morning one pig was found dead, and within three weeks all of this second group had died just as the first had done. Segregating the sick animals did not save the others.” The authors commented, “…this epidemic among the animals … was so strikingly similar to the influenza epidemic in man” [65].

    Given the apparent spread of 1918 pandemic influenza virus among guinea pigs in the Camp Cody colony, Palese wondered whether the species might, like ferrets, be a model for studying influenza virus transmission (P Palese, personal communication). His laboratory went on to demonstrate that commercially available, outbred Hartley strain guinea pigs could be productively infected with an unadapted human isolate by intranasal inoculation and could transmit the virus both to uninfected cage-mates and to naïve guinea pigs in cages up to 91 cm (3 feet) away [50]. Inbred Strain 2 and Strain 13 guinea pigs were similarly susceptible to infection with human influenza virus strains and could transmit virus to susceptible partner animals; however, inbred colonies are privately held and are less readily procured than are commercially bred Hartley guinea pigs [50, 52, 66]. Further research by the Palese group has demonstrated the presence of antibodies to human influenza viruses in livestock guinea pigs raised in three different regions of Ecuador, where guinea pig meat (cuy) is part of the traditional Andean cuisine [67]. Although influenza viruses seem not to be enzootic in guinea pigs, they do appear capable of jumping the species barrier from infected human farmers into their livestock guinea pigs and may also circulate among guinea pig herds under non-experimental conditions. However, influenza virus spread among guinea pigs outside of the lab has yet to be documented, likely because the absence of clinical signs of infection makes identifying influenza outbreaks in livestock herds more challenging [67].

    Thus, the main disadvantage of the guinea pig model is that, unlike ferrets, guinea pigs show minimal clinical evidence of influenza virus infection [2, 68, 69], even remaining overtly unaffected by infection with HPAI strains that are fatal to mice and ferrets [70, 71]. Further research is needed to understand the role of symptomatology in influenza virus transmission in both animal models and in humans, in whom subclinical infection and asymptomatic virus shedding may be underappreciated [72, 73].

    Go to:
    Guinea pig modeling of influenza virus transmission: Key discoveries
    Complementing Schulman’s finding that rapid airflow speed decreases influenza virus transmission among mice, a few observations regarding airflow have been made in the guinea pig model. In their initial guinea pig transmission experiments, the Palese group noted that influenza virus transmission could occur over distances up to 91 cm, but that “…transmission was not observed when the relative positions of the infected and uninfected animals were reversed, suggesting that spread depended on the direction of airflow in the room” [50]. Subsequent experiments, performed in environmentally controlled chambers with an upward directional airflow, demonstrated influenza virus transmission when uninfected guinea pigs were placed 100 cm above infected animals, against gravity but with the chambers’ intrinsic airflow [52].

    The Palese group also studied the effects of relative humidity (RH) and temperature on influenza virus transmission in the environmentally controlled chambers. At various combinations of temperature (5, 20, or 30°C) and RH (20, 35, 50, 65, and 80%), the transmission efficiency of A/Panama/2007/1999(H3N2) increased as temperature decreased, with a similar general trend towards increased transmission efficiency was observed with decreasing humidity [49, 51, 74], similar to that observed by Schulman in the mouse model [45]. The same inverse correlation between transmission efficiency and ambient temperature has since been demonstrated in influenza A(H1N1), A(H1N1pdm09), and influenza B viruses [74–76]. Of note, guinea pigs can transmit influenza B viruses, which has yet to be demonstrated in ferrets [76].

    Go to:
    Concluding remarks
    Many mammalian animal models have been used in influenza virus transmission research, including cotton rats, Syrian hamsters, cats, dogs, domestic pigs, and non-human primates. In this review, we have discussed ferrets, mice, and guinea pigs, the three models used most frequently in the past and currently.

    Like humans, seasonal influenza in the ferret is manifested by fever, nasal discharge, lethargy, anorexia, and sneezing, while infection with HPAI viruses can result in severe disease and death. Because influenza is not clinically apparent in guinea pigs, they cannot be used to study interventions designed to reduce morbidity or mortality. However, both models are readily susceptible to infection with human influenza virus isolates, demonstrating robust viral replication and efficient transmission of virus to others of their species. In contrast, human influenza viruses are poorly infectious in mice, requiring the use of previously mouse-adapted strains. Even after adaptation, though, inconsistent results have been obtained when assessing the transmissibility of mouse-infecting strains such as PR8, WSN, and A/Japan/305/1957.

    The main drawback to the ferret as a model for influenza virus transmission is its cost, due to its relatively lower commercial availability, larger size, and more complex husbandry requirements, and adequately powered experiments can be costly to achieve. Statistically robust data can, however, be obtained at less expense in rodent models.

    Thus, there are a variety of animal models in which to study the transmission of influenza viruses, each with advantages and disadvantages that must be understood and considered when designing and performing influenza virus transmission experiments in animal models.

    © Copyright Original Source



    Am I the only one who dislikes a quoted wall of text from any poster on any given subject? More so if some ass then quotes the whole thing and only responds with only a small paragraph of a reply or less that barely touches on the topic?

  10. Amen Cerebrum123 amen'd this post.
  11. #220
    tWebber Starlight's Avatar
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    Quote Originally Posted by EvoUK View Post
    Am I the only one who dislikes a quoted wall of text from any poster on any given subject? More so if some ass then quotes the whole thing and only responds with only a small paragraph of a reply or less that barely touches on the topic?
    Is that an ironic self-description of your post?

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