2009 H1N1 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). 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.

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 H3N2 subtypes are circulating in the U.S. swine population.

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.

Recent ARS Research Results: 2009 H1N1 Influenza Virus

Project 1: Serologic cross-reactivity of serum samples from U.S pigs against the new 2009 H1N1 influenza virus

This study addressed whether U.S commercial swine herds are susceptible to the 2009 A/H1N1 influenza viruses isolated from persons in California, New York, and Mexico. ARS researchers tested serum samples from pigs inoculated with swine influenza viruses that are known to circulate in the U.S or vaccinated with commercial vaccines to determine if U.S commercial swine herds are susceptible to the new H1N1 influenza virus. They found that there was limited cross reactivity against the new 2009 A/H1N1 influenza viruses. This suggests that pre-existing immunity induced by swine influenza viruses previously circulating in the U.S may not protect pigs against the new 2009 A/H1N1 influenza viruses presently circulating in people. Importantly, vaccines currently used to protect pigs on U.S swine farms operations against swine influenza viruses may not be effective against the new 2009 A/H1N1 influenza viruses.

Next step: ARS scientists will test the efficacy of a select subset of swine influenza virus vaccines tested in this first study, and evaluate their effectiveness in a pig vaccination challenge study to determine whether measurable antibody titers in pigs correlate with protection against the new A/H1N1 Influenza Virus.

More information about this study

Project 2: Four-pig pathogenesis study with the 2009 A/H1N1 influenza virus

This study addressed whether meat, blood, and tissue from pigs infected with the new 2009 A/H1N1 influenza virus are free of infectious virus. ARS researchers tested four 5-week-old cross-bred pigs from a herd free of swine influenza virus. The pigs were inoculated with an infective dose of the 2009 A/H1N1 influenza virus isolated from persons in California. Pigs were observed daily for clinical signs of disease and nasal swabs and fresh samples from lung, tonsil, inguinal lymph node, liver, spleen, kidney, skeletal muscle (ham), and colon contents were tested by the most sensitive virus detection assays. Live 2009 A/H1N1 influenza virus was only detected in the respiratory tract of infected pigs and the virus did not appear to spread and replicate in other tissues.

Next step: ARS scientists will conduct a larger study to evaluate tissues at additional time points (1, 3, 5, and 7 days dpi).

More information about this study

ARS Swine Influenza Research Program

The ARS research program focuses on tracking the evolution of swine influenza viruses and their potential impact on the swine industry. The Agency also tracks the ability of current vaccines to protect swine from new virus isolates.

Because of the emergence of novel influenza viruses in U.S. pigs, USDA-ARS at NADC in collaboration with USDA's Animal and Plant Health Inspection Service and CDC created an interagency agreement in 2008 to address the need for monitoring the swine influenza virus. Having this agreement already in place has enabled the rapid response to evaluate the zoonotic potential of the 2009 H1N1 influenza virus.

ARS also supports a proposed USDA-APHIS swine influenza surveillance program by providing additional characterization of emerging swine influenza virus (SIV) isolates as they are identified through the surveillance program.

ARS Research Projects

Genetic and Antigenic Characterization of North American H1 Swine Influenza Viruses

Study of Influenza A Viruses

Characterization of Swine Influenza Virus Isolates

Influenza Pandemic Preparedness

ARS Publications

The Role of Swine in the Generation of Novel Influenza Viruses

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

Swine Influenza Viruses: A North American Perspective

Protection of Weaned Pigs by Vaccination with Human Adenovirus 5 Recombinant Viruses Expressing the Hemagglutinin and the Nucleoprotein of H3N2 Swine Influenza Virus

The Roles of Influenza Virus Haemagglutinin and Nueleoprotein in Protection: Analysis Using Vaccinia Virus Recombinants

Overcoming Maternal Antibody Interference by Vaccination with Human Adenovirus 5 Recombinant Viruses Expressing the Hemagglutinin and the Nucleoprotein of Swine Influenza Virus

Isolation of Reassortant H2N3 Avian/Swine Influenza Virus from Pigs in the United States

Limited Susceptibility and Lack of Systemic Infection by an H3N2 Swine Influenza Virus In Intranasally Inoculated Chickens

Failure of Protection And Enhanced Pneumonia with a US H1N2 Swine Influenza Virus in Pigs Vaccinated With an Inactivated Classical Swine H1N1 Vaccine