Trends in Microbiology
Volume 23, Issue 3, March 2015, Pages 142-153
Journal home page for Trends in Microbiology

Review
Reverse zoonosis of influenza to swine: new perspectives on the human–animal interface

https://doi.org/10.1016/j.tim.2014.12.002Get rights and content

Highlights

  • Humans transmit far more influenza viruses to swine than swine transmit to humans.

  • Human-to-swine transmission is key to the evolution of influenza diversity in swine.

  • In effect, humans sow the seeds of future pandemics by infecting pigs.

  • A balanced view of the bidirectional nature of the human–animal interface is needed.

The origins of the 2009 influenza A (H1N1) pandemic in swine are unknown, highlighting gaps in our understanding of influenza A virus (IAV) ecology and evolution. We review how recently strengthened influenza virus surveillance in pigs has revealed that influenza virus transmission from humans to swine is far more frequent than swine-to-human zoonosis, and is central in seeding swine globally with new viral diversity. The scale of global human-to-swine transmission represents the largest ‘reverse zoonosis’ of a pathogen documented to date. Overcoming the bias towards perceiving swine as sources of human viruses, rather than recipients, is key to understanding how the bidirectional nature of the human–animal interface produces influenza threats to both hosts.

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

References (135)

  • Y. Guo

    Characterization of a new avian-like influenza A virus from horses in China

    Virology

    (1992)
  • G. Zhang

    Identification of an H6N6 swine influenza virus in southern China

    Infect. Genet. Evol.

    (2011)
  • T.Y. Kwon

    Genetic characterization of H7N2 influenza virus isolated from pigs

    Vet. Microbiol.

    (2011)
  • H. Yu

    Genetic diversity of H9N2 influenza viruses from pigs in China: a potential threat to human health?

    Vet. Microbiol.

    (2011)
  • B.Z. Löndt

    Failure to infect pigs co-housed with ducks or chickens infected experimentally with A/turkey/Turkey/1/2005 (H5N1) highly pathogenic avian influenza virus

    Vet. Microbiol.

    (2013)
  • D.M. Morens

    H7N9 avian influenza A virus and the perpetual challenge of potential human pandemicity

    MBio

    (2013)
  • C. Scholtissek

    Pigs as the ‘mixing vessel’ for the creation of new pandemic influenza A viruses

    Med. Princ. Pract.

    (1990)
  • H. Kida

    Potential for transmission of avian influenza viruses to pigs

    J. Gen. Virol.

    (1994)
  • W. Ma

    The role of swine in the generation of novel influenza viruses

    Zoonoses Public Health

    (2009)
  • R.J. Garten

    Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans

    Science

    (2009)
  • S. Epperson

    Human infections with influenza A(H3N2) variant virus in the United States, 2011–2012

    Clin. Infect. Dis.

    (2013)
  • R.G. Webster

    Evolution and ecology of influenza A viruses

    Microbiol. Rev.

    (1992)
  • R.G. Webster et al.

    The origin of pandemic influenza

    Bull. World Health Organ.

    (1972)
  • Y. Kawaoka

    Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics

    J. Virol.

    (1989)
  • R.G. Scholtens

    U.S. Epizootic of equine influenza, 1963

    Public Health Rep.

    (1964)
  • P.C. Crawford

    Transmission of equine influenza virus to dogs

    Science

    (2005)
  • V. Shinde

    Triple-reassortant swine influenza A (H1) in humans in the United States, 2005–2009

    N. Engl. J. Med.

    (2009)
  • P.N.Q. Pascua

    Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

    Proc. Natl. Acad. Sci. U.S.A.

    (2012)
  • S. Barman

    Pathogenicity and transmissibility of North American triple reassortant swine influenza A viruses in ferrets

    PLoS Pathog.

    (2012)
  • A. Pereda

    Pandemic (H1N1) 2009 outbreak on pig farm, Argentina

    Emerg. Infect. Dis.

    (2010)
  • J. Cappuccio et al.

    Outbreak of swine influenza in Argentina reveals a non-contemporary human H3N2 virus highly transmissible among pigs

    J. Gen. Virol.

    (2011)
  • D.S. Rajão

    Genetic characterization of influenza virus circulating in Brazilian pigs during 2009 and 2010 reveals a high prevalence of the pandemic H1N1 subtype

    Influenza Other Respir. Viruses

    (2012)
  • G.C. Ramirez-Nieto

    First isolation and identification of H1N1 swine influenza viruses in Colombian pig farms

    Health (Irvine. Calif).

    (2012)
  • K. Nagarajan

    Influenza A H1N1 virus in Indian pigs & its genetic relatedness with pandemic human influenza A 2009 H1N1

    Indian J. Med. Res.

    (2010)
  • H.K.K. Perera

    Swine influenza in Sri Lanka

    Emerg. Infect. Dis.

    (2013)
  • P.K. Holyoake

    The first identified case of pandemic H1N1 influenza in pigs in Australia

    Aust. Vet. J.

    (2011)
  • Y. Deng

    Transmission of influenza A (H1N1) 2009 pandemic viruses in Australian swine

    Influenza Other Respir. Viruses

    (2012)
  • D.M. Morens et al.

    Historical thoughts on influenza viral ecosystems, or behold a pale horse, dead dogs, failing fowl, and sick swine

    Influenza Other Respir. Viruses

    (2010)
  • J.S. Koen

    A practical method for field diagnosis of swine diseases

    Am. J. Vet. Med.

    (1919)
  • M. Worobey

    A synchronized global sweep of the internal genes of modern avian influenza virus

    Nature

    (2014)
  • R.E. Shope

    The etiology of swine influenza

    Science

    (1931)
  • H. Zhu

    History of Swine influenza viruses in Asia

    Curr. Top. Microbiol. Immunol.

    (2013)
  • I.H. Brown

    History and epidemiology of swine influenza in Europe

    Curr. Top. Microbiol. Immunol.

    (2013)
  • A. Lorusso

    Contemporary epidemiology of North American lineage triple reassortant influenza A viruses in pigs

    Curr. Top. Microbiol. Immunol.

    (2013)
  • K. Ottis

    Human influenza A viruses in pigs: isolation of a H3N2 strain antigenically related to A/England/42/72 and evidence for continuous circulation of human viruses in the pig population

    Arch. Virol.

    (1982)
  • C. Olsen

    Virologic and serologic surveillance for human, swine and avian influenza virus infections among pigs in the north-central United States

    Arch. Virol.

    (2000)
  • A. Karasin

    Identification of human H1N2 and human–swine reassortant H1N2 and H1N1 influenza A viruses among pigs in Ontario, Canada (2003 to 2005)

    J. Clin. Microbiol.

    (2006)
  • M.I. Nelson

    Introductions and evolution of human-origin seasonal influenza A viruses in multinational swine populations

    J. Virol.

    (2014)
  • K. Howden et al.

    An investigation into human pandemic influenza virus (H1N1) 2009 on an Alberta swine farm

    Can. Vet. J.

    (2009)
  • S. Forgie et al.

    Swine outbreak of pandemic influenza A virus on a Canadian research farm supports human-to-swine transmission

    Clin. Infect. Dis.

    (2011)
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