ARS Home » Office of Communications » Br » H1N1 » index

Influenza A Virus

Soon after the emergence of the H1N1 virus in April 2009, ARS scientists at the National Animal Disease Center in Ames, Iowa, began research using virus samples provided by the Centers for Disease Control and Prevention (CDC). Shortly after the reports of the new H1N1 virus in North America, H1N1 virus outbreaks were reported on turkey breeder farms in Virginia and California in the United States as well as in Chile, Canada, and France. ARS scientists at the Southeast Poultry Research Laboratory (SEPRL) quickly evaluated the pathogenesis of the new H1N1 virus in bird species to determine the potential risk to the poultry industry. The first step was to evaluate whether current U.S H1N1 swine influenza vaccines can protect pigs from infection with the 2009 H1N1 influenza virus circulating in people. This research study also evaluated whether pre-existing titers in pigs previously infected with endemic H1N1 swine influenza viruses circulating in the U.S could protect against the 2009 H1N1 influenza virus. Second was to address whether meat, blood and tissue from pigs infected with the new 2009 H1N1 Influenza A Virus would be free of infectious virus.

Classical swine influenza virus infections are enzootic among pigs in North America. Sporadic cases of human infection with swine influenza virus have been reported in the United States and elsewhere. Worldwide, more than 50 human cases of swine influenza virus infection, mostly due to classical swine influenza virus, have been documented in the past 35 years, with the greatest risk of infection among people with occupational exposure to live pigs.

Experts believe pigs can act as a "mixing vessel" for the reassortment of avian, swine and human influenza viruses, and might play an important role in the emergence of novel influenza viruses that could be capable of causing a human pandemic similar to the virus in the current outbreak.

ARS Veterinary Medical Officers Amy Vincent and Kelly Lager are leading ARS's swine influenza virus research program

Between the 1930s and the 1990s, the most commonly circulating swine influenza virus among pigs-classical swine influenza A, known as H1N1-underwent little change.

However, by the late 1990s, multiple strains and subtypes of triple reassortant swine influenza viruses-whose genomes include combinations of avian, human and swine influenza virus gene segments-had emerged and became predominant among North American pigs. The 2009 H1N1 influenza virus is also a triple reassortent, but its lineage is different than the H1N1 influenza viruses currently circulating in U.S. pigs.

Background

The genetic makeup of swine influenza viruses is identical to other influenza A viruses and consists of 8 segments of RNA that code for different proteins. Influenza viruses have the ability to exchange these segments, creating new genetically different viruses. Two major surface glycoproteins (proteins with a carbohydrate attached), called hemagglutinin (H) and neuraminidase (N), are how influenza A viruses are identified. These glycoproteins also determine the host range, antigenicity and the pathogenicity of the viruses. The hemagglutinin and neuraminidase proteins are important targets for diagnostics and used to designate the subtype of the virus.

Currently 16 different hemagglutinins and 9 neuraminidases have been identified. The majority of these viral subtypes are found in waterfowl, with only a few combinations being found in humans and swine.

Swine influenza virus (SIV) is one of the primary causes of respiratory disease in growing pigs and can lead to major economic losses. Currently, only H1N1, H1N2, and pN2 subtypes are circulating in the U.S. swine population.

For more information about ARS research on H1N1 (swine) influenza viruses, contact:

Cyril Gay, ARS Senior National Program Leader, Animal Health cyril.gay@ars.usda.gov 301-504-4786

Pigs have long been considered a potential source for new and novel influenza viruses that infect humans, as they have receptors on their cells that bind both mammalian and avian influenza viruses, increasing the opportunity for the exchange of genetic segments of the virus.

Previously, the CDC have reported approximately one case of human infection with a swine influenza virus every one to two years.

ARS Research Publications

Influenza Viruses in Swine

Contemporary Epidemiology of North American Lineage Triple Reassortant Influenza A Viruses in Pigs. Lorusso A, Vincent AL, Gramer MR, Lager KM, Ciacci-Zanella JR (2012) Current Topics in Microbiology and Immunology (In press)

Pathogenicity of swine influenza viruses possessing an avian or swine-origin PB2 polymerase gene evaluated in mouse and pig models. Ma W, Lager KM, Li X, Janke BH, Mosier DA, Painter LE, Ulery ES, Ma J, Lekcharoensuk P, Webby RJ, Richt JA (2011) Virology 410:1-6

Influenza virus coinfection with Bordetella bronchiseptica enhances bacterial colonization and host responses exacerbating pulmonary lesions. Loving CL, Brockmeier SL, Vincent AL, Palmer MV, Sacco RE, Nicholson TL (2010) Microbial Pathogenesis 49:237-245

More information about the HINI (swine) influenza virus:

The Role of Swine in the Generation of Novel Influenza Viruses. Ma W, Lager KM, Vincent AL, Janke BH, Gramer MR, Richt JA (2009) Zoonoses Public Health 56:326-337. Review.

Global transmission of influenza viruses from humans to swine. Nelson MI, Gramer MR, Vincent AL, Holmes EC (2012) Journal of General Virology Jul 18. [Epub ahead of print]

Spatial dynamics of human-origin H1 influenza A virus in North American swine. Nelson MI, Lemey P, Tan Y, Vincent A, Lam TT, Detmer S, Viboud C, Suchard MA, Rambaut A, Holmes EC, Gramer M (2011) PLoS Pathogens 7:e1002077

Swine influenza viruses a North American perspective. Vincent AL, Ma W, Lager KM, Janke BH, Richt JA (2008) Advances in Virus Research 72:127-154

Exposure of sero-positive gilts to swine influenza virus may cause a few stillbirths per litter. Wesley RD (2004) Canadian Journal of Veterinary Research 68:215-217

H1N1 Research in Pigs

Restored PB1-F2 into the 2009 Pandemic H1N1 Influenza Virus has minimal effects in swine. Pena L, Vincent AL, Loving CL, Henningson JN, Lager KM, Lorusso A, Perez DR (2012) Journal of Virology 86:5523-32

A novel monoclonal antibody effective against lethal challenge with swine-lineage and 2009 pandemic H1N1 influenza viruses in mice. Shao H, Ye J, Vincent AL, Edworthy N, Ferrero A, Qin A, Perez DR (2011) Virology 417:379-384

Characterization of H1N1 swine influenza viruses circulating in Canadian pigs in 2009. Nfon CK, Berhane Y, Hisanaga T, Zhang S, Handel K, Kehler H, Labrecque O, Lewis NS, Vincent AL, Copps J, Alexandersen S, Pasick J (2011) Journal of Virology 85:8667-8679

Genetic and antigenic characterization of H1 influenza viruses from United States swine from 2008. Lorusso A, Vincent AL, Harland ML, Alt D, Bayles DO, Swenson SL, Gramer MR, Russell CA, Smith DJ, Lager KM, Lewis NS (2011) The Journal of General Virology 92:919-930

Receptor specificity of subtype H1 influenza A viruses isolated from swine and humans in the United States. Chen LM, Rivailler P, Hossain J, Carney P, Balish A, Perry I, Davis CT, Garten R, Shu B, Xu X, Klimov A, Paulson JC, Cox NJ, Swenson S, Stevens J, Vincent A, Gramer M, Donis RO (2011) Virology 412:401-410

Experimental inoculation of pigs with pandemic H1N1 2009 virus and HI cross-reactivity with contemporary swine influenza virus antisera. Vincent AL, Lager KM, Faaberg KS, Harland M, Zanella EL, Ciacci-Zanella JR, Kehrli ME, Jr., Janke BH, Klimov A (2010) Influenza and Other Respiratory Viruses 4:53-60

Efficacy of inactivated swine influenza virus vaccines against the 2009 A/H1N1 influenza virus in pigs. Vincent AL, Ciacci-Zanella JR, Lorusso A, Gauger PC, Zanella EL, Kehrli ME, Jr., Janke BH, Lager KM (2010) Vaccine 28:2782-2787

Identification and characterization of a highly virulent triple reassortant H1N1 swine influenza virus in the United States. Ma W, Vincent AL, Lager KM, Janke BH, Henry SC, Rowland RR, Hesse RA, Richt JA (2010) Virus Genes 40:28-36

Characterization of an influenza A virus isolated from pigs during an outbreak of respiratory disease in swine and people during a county fair in the United States. Vincent AL, Swenson SL, Lager KM, Gauger PC, Loiacono C, Zhang Y (2009) Veterinary Microbiology 137:51-59

Characterization of a newly emerged genetic cluster of H1N1 and H1N2 swine influenza virus in the United States. Vincent AL, Ma W, Lager KM, Gramer MR, Richt JA, Janke BH (2009) Virus Genes 39:176-185

Absence of 2009 pandemic H1N1 influenza A virus in fresh pork. Vincent AL, Lager KM, Harland M, Lorusso A, Zanella E, Ciacci-Zanella JR, Kehrli ME, Jr., Klimov A (2009) PLoS ONE 4:e8367

Evaluation of hemagglutinin subtype 1 swine influenza viruses from the United States. Vincent AL, Lager KM, Ma W, Lekcharoensuk P, Gramer MR, Loiacono C, Richt JA (2006) Veterinary Microbiology 118:212-222

pN2 and Related Research in Pigs

Strain-dependent Effects of PB1-F2 of Triple Reassortant pN2 Influenza Viruses in Swine. Pena L, Vincent AL, Loving CL, Henningson JN, Lager KM, Perez DR (2012) Journal of General Virology Jul 18. [Epub ahead of print]

Evolution of Novel Reassortant A/pN2 Influenza Viruses in North American Swine and Humans, 2009-2011. Nelson MI, Vincent AL, Kitikoon P, Holmes EC, Gramer MR (2012) Journal of Virology 86:8872-8878

Global transmission of influenza viruses from humans to swine. Nelson MI, Gramer MR, Vincent AL, Holmes EC (2012) Journal of General Virology Jul 18. [Epub ahead of print]

Pathogenicity and transmission in pigs of the novel A(pN2)v influenza virus isolated from humans and characterization of swine pN2 viruses isolated in 2010-2011. Kitikoon P, Vincent AL, Gauger PC, Schlink SN, O.Bayles D, Gramer MR, Darnell D, Webby RJ, M.Lager K, Swenson SL, Klimov A (2012) Journal of Virology 86:6804-6814

Novel swine influenza virus subtype pN1, United States. Lekcharoensuk P, Lager KM, Vemulapalli R, Woodruff M, Vincent AL, Richt JA (2006) Emerging infectious diseases 12:787-794

Pathogenic and antigenic properties of phylogenetically distinct reassortant pN2 swine influenza viruses cocirculating in the United States Richt JA, Lager KM, Janke BH, Woods RD, Webster RG, Webby RJ (2003). Journal of Clinical Microbiology 41:3198-3205

Avian Influenza Virus Research in Pigs

Weingartl HM, Albrecht RA, Lager KM, Babiuk S, Marszal P, Neufeld J, Embury-Hyatt C, Lekcharoensuk P, Tumpey TM, Garcia-Sastre A, Richt JA (2009) Experimental infection of pigs with the human 1918 pandemic influenza virus. Journal of Virology 83:4287-4296

Domestic pigs have low susceptibility to pN1 highly pathogenic avian influenza viruses. Lipatov AS, Kwon YK, Sarmento LV, Lager KM, Spackman E, Suarez DL, Swayne DE (2008) PLoS Pathogens 4:e1000102

Identification of H2N3 influenza A viruses from swine in the United States. Ma W, Vincent AL, Gramer MR, Brockwell CB, Lager KM, Janke BH, Gauger PC, Patnayak DP, Webby RJ, Richt JA (2007) Proceedings of the National Academy of Sciences USA 104:20949-20954

Swine Influenza Diagnostics Research

Nicholson TL, Kukielka D, Vincent AL, Brockmeier SL, Miller LC, Faaberg KS (2011) Utility of a panviral microarray for detection of swine respiratory viruses in clinical samples. Journal of Clinical Microbiology 49:1542-1548

Shao H, Ye J, Vincent AL, Song H, Hickman D, Qin A, Lamichhane C, Perez DR (2011) A monoclonal antibody-based ELISA for differential diagnosis of 2009 pandemic H1N1. Influenza and Other Respiratory Viruses 5 Suppl 1:138-141

Lorusso A, Faaberg KS, Killian ML, Koster L, Vincent AL (2010) One step real-time RT-PCR for pandemic influenza A virus (H1N1) 2009 matrix gene detection in swine samples. Journal of Virological Methods 164:83-87

Ciacci-Zanella JR, Vincent AL, Prickett JR, Zimmerman SM, Zimmerman JJ (2010) Detection of anti-influenza A nucleoprotein antibodies in pigs using a commercial influenza epitope-blocking enzyme-linked immunosorbent assay developed for avian species. Journal of Veterinary Diagnostic Investigation 22:3-9

Quan PL, Palacios G, Jabado OJ, Conlan S, Hirschberg DL, Pozo F, Jack PJ, Cisterna D, Renwick N, Hui J, Drysdale A, Amos-Ritchie R, Baumeister E, Savy V, Lager KM, Richt JA, Boyle DB, Garcia-Sastre A, Casas I, Perez-Brena P, Briese T, Lipkin WI (2007) Detection of respiratory viruses and subtype identification of influenza A viruses by GreeneChipResp oligonucleotide microarray. Journal of Clinical Microbiology 45:2359-2364

Richt JA, Lager KM, Clouser DF, Spackman E, Suarez DL, Yoon KJ (2004) Real-time reverse transcription-polymerase chain reaction assays for the detection and differentiation of North American swine influenza viruses. Journal of Veterinary Diagnostic Investigation 16:367-373

Swine Influenza Vaccine Research

H1N1 virus

Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A/H1N1 influenza virus. Gauger PC, Vincent AL, Loving CL, Henningson JN, Lager KM, Janke BH, Kehrli ME, Jr, Roth JA (2012) Veterinary Pathology Mar 28. [Epub ahead of print] In Press

Intranasal vaccination with replication defective adenovirus-5 encoding influenza hemagglutinin elicits protective immunity to homologous challenge and partial protection to heterologous challenge in pigs. Braucher DR, Henningson JN, Loving CL, Vincent AL, Kim E, Steitz J, Gambotto AA, Kehrli ME, Jr (2012) Clinical and Vaccine Immunology Aug 29 [Epub ahead of print]

Live attenuated influenza vaccine provides superior protection from heterologous infection in pigs with maternal antibodies without inducing vaccine associated enhanced respiratory disease. Vincent AL, Ma W, Lager KM, Richt JA, Janke BH, Sandbulte MR, Gauger P, Loving CL, Webby RJ, Garcia-Sastre A (2012) Journal of Virology Jul 18 [Epub ahead of print]

Heightened adaptive immune responses following vaccination with a temperature-sensitive, live-attenuated influenza virus compared to adjuvanted, whole-inactivated virus in pigs Loving CL, Vincent AL, Pena L, Perez DR (2012). Vaccine 30(40):5830-8

Vaccination with NS1-truncated pN2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs. Kappes MA, Sandbulte MR, Platt R, Wang C, Lager KM, Henningson JN, Lorusso A, Vincent AL, Loving CL, Roth JA, Kehrli ME, Jr. (2012) Vaccine 30:280-288

Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (?-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus. Gauger PC, Vincent AL, Loving CL, Lager KM, Janke BH, Kehrli ME, Jr., Roth JA (2011) Vaccine 29:2712-2719

Comparison of humoral and cellular immune responses to inactivated swine influenza virus vaccine in weaned pigs. Platt R, Vincent AL, Gauger PC, Loving CL, Zanella EL, Lager KM, Kehrli ME, Jr., Kimura K, Roth JA (2011) Veterinary Immunology and Immunopathology 142:252-257

Modifications in the polymerase genes of a swine-like triple reassortant influenza virus to generate live attenuated vaccines against 2009 pandemic H1N1 viruses. Pena L, Vincent AL, Ye J, Ciacci-Zanella JR, Angel M, Lorusso A, Gauger PC, Janke BH, Loving CL, Donis R, O'Neill E, Perez DR (2011) Journal of Virology 85:456-469

DNA Vaccination Elicits Protective Immune Responses against Pandemic and Classic Swine Influenza Viruses in Pigs. Gorres JP, Lager KM, Kong W-P, Royals M, Todd JP, Vincent AL, Wei C-J, Loving CL, Zanella EL, Janke B, Marcus E. Kehrli J, Nabel GJ, Rao SS (2011) Clinical and Vaccine Immunology 18:1987-1995

Vaccine efficacy and immune response to swine influenza virus challenge in pigs infected with porcine reproductive and respiratory syndrome virus at the time of SIV vaccination. Kitikoon P, Vincent AL, Jones KR, Nilubol D, Yu S, Janke BH, Thacker BJ, Thacker EL (2009) Veterinary Microbiology 139:235-244

Swine influenza matrix 2 (M2) protein contributes to protection against infection with different H1 swine influenza virus (SIV) isolates. Kitikoon P, Vincent AL, Janke BH, Erickson B, Strait EL, Yu S, Gramer MR, Thacker EL (2009) Vaccine 28:523-531

Failure of protection and enhanced pneumonia with a US H1N2 swine influenza virus in pigs vaccinated with an inactivated classical swine H1N1 vaccine. Vincent AL, Lager KM, Janke BH, Gramer MR, Richt JA (2008) Veterinary Microbiology 126:310-323

Efficacy of intranasal administration of a truncated NS1 modified live influenza virus vaccine in swine. Vincent AL, Ma W, Lager KM, Janke BH, Webby RJ, Garcia-Sastre A, Richt JA (2007) Vaccine 25:7999-8009

Vaccination of pigs against swine influenza viruses by using an NS1-truncated modified live-virus vaccine. Richt JA, Lekcharoensuk P, Lager KM, Vincent AL, Loiacono CM, Janke BH, Wu WH, Yoon KJ, Webby RJ, Solorzano A, Garcia-Sastre A (2006) Journal of Virology 80:11009-11018

Overcoming maternal antibody interference by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of swine influenza virus. Wesley RD, Lager KM (2006) Veterinary Microbiology 118:67-75

Evaluation of a recombinant human adenovirus-5 vaccine administered via needle-free device and intramuscular injection for vaccination of pigs against swine influenza virus. Wesley RD, Lager KM (2005) Am J Vet Res 66:1943-1947

Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs. Solorzano A, Webby RJ, Lager KM, Janke BH, Garcia-Sastre A, Richt JA (2005) Journal of Virology 79:7535-7543

Protection of weaned pigs by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of pN2 swine influenza virus. Wesley RD, Tang M, Lager KM (2004) Vaccine 22:3427-3434

Related Graphics

Epidemiology of SIVs in North America. Chronology of transmission. Click the image for larger version.

Diagram of viruses with their 8 gene segment constellations in currently circulating SIVs. Click the image for larger version.

H1N1 Take Home MessageClick the image for larger version.