Trends in Microbiology
ReviewReverse zoonosis of influenza to swine: new perspectives on the human–animal interface
Section snippets
Swine as reservoirs for IAV diversity and pandemic threats
IAVs are considered to be one of the greatest threats for the next global pandemic given the abundance of permanent animal reservoirs harboring viruses that occasionally spill over into humans [1]. For decades, swine have been thought to serve as intermediate ‘mixing-vessel’ hosts (see Glossary) for the evolution of pandemic viruses because of their capacity to be infected with both avian and human influenza viruses, which can exchange genome segments via a process termed ‘reassortment’ to
Humans as major sources of influenza virus diversity in swine
While there is historical evidence for influenza outbreaks in humans, poultry, horses, and even canines dating back several centuries [28], there is evidence of only one possible localized influenza virus outbreak in swine in England before the 1918 H1N1 ‘Spanish flu’ pandemic [29]. During the early stages of the 1918 pandemic, outbreaks of the virus were identified in both humans and swine in the USA [30], and it remains impossible to determine whether humans first transmitted the virus to
Large-scale reverse zoonosis of pH1N1 viruses
On May 2, 2009, approximately 1 month after the pH1N1 virus was detected in humans, pH1N1 was isolated from the first pig on a farm in Alberta, Canada, in what was eventually determined to be the first documented case of human-to-swine transmission of pH1N1 43, 44. Since then, the pH1N1 virus has transmitted repeatedly from humans to swine spanning six continents (Table 1, Figure 4), in what is arguably the largest global occurrence of reverse zoonosis of any infectious disease that has been
Refining models of IAV ecology
The relatively lower barrier of cross-species transmission of pH1N1 from humans back to swine, compared to other human viruses, may be explained in part by the fact that pH1N1 was originally a swine virus. Even so, the human-adapted pH1N1 shows little evidence of transmitting from swine back to humans, at least in terms of stable introductions with onward human-to-human transmission [45]. Direct comparisons of the frequency of human-to-swine versus swine-to-human IAV transmission remains
Questions about the ecology of human-to-swine transmission
Compared to the extensive study of the zoonotic transmission of H3N2v viruses from swine to humans 86, 87, including the capacity of swine with asymptomatic influenza infections to efficiently transmit viruses to humans, mainly children, within the agricultural fair setting [88], relatively little is known about the ecological and immunological circumstances under which human IAVs transmit to swine. This lack of understanding undermines efforts to evaluate potential biosecurity measures, such
Human-origin viral diversity reduces efficacy of swine influenza vaccines
The repeated introduction of human-origin viral diversity, particularly in the form of multiple antigenically distinct co-circulating HA and NA proteins, has greatly complicated the development of effective vaccines for the control of influenza in swine. In the USA vaccines are used primarily in sows to provide passive antibody to piglets and, to a lesser extent, during the grow/finish phase of production to decrease disease, lung lesions, and transmission 89, 90. One of the commercially
The future of swIAV surveillance and research
Despite the evidence, it remains counterintuitive to view humans as major sources of disease for swine. This bias is perpetuated by the imbalance in surveillance in humans versus swine (Figure 1), and this obscures an accurate understanding of the viral ecology, in which humans and swine exchange pathogens in both directions. Sample bias continues to be a major impediment to understanding swIAV evolution and diversity, including capturing the full scale of human-to-swine transmission. Major
Concluding remarks
Recognizing the important role of human-to-swine transmission in the evolution of swIAV diversity requires that we refine our concept of the ‘mixing vessel’ (Figure 5B), which has perpetuated an over-simplified understanding of IAV ecology. Swine can be considered as mixing vessels in the sense that pigs are more capable than humans of harboring a large number of co-circulating IAV lineages that can generate diverse combinations of segments via reassortment. However, at this time there is
Acknowledgments
We would like to thank National Institutes of Health (NIH) intern Adaeze Ezeofor for her contributions to the organization and identification of the many journal references cited in this manuscript. We are also grateful to Drs Cecile Viboud (NIH) and Edward C. Holmes (University of Sydney) for their insightful comments on earlier drafts of this manuscript. This research was conducted within the context of the Multinational Influenza Seasonal Mortality Study (MISMS) (http://www.origem.info/misms/
Glossary
- Antigenic drift
- the continual evasion of host immunity by the gradual accumulation of mutations in the hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins that change the antigenic structure of the influenza A virus (IAV).
- Bayesian phylogeography
- the inference of viral migration patterns using time-scaled phylogenies inferred in a Bayesian framework in which prior knowledge assesses the probability of model parameters in the presence of new data.
- Hemagglutinin (HA)
- an influenza virus
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