The Changing Face of Swine Influenza Virus

Flu in pigs has been known for 90 years, and on the surface, it may appear as though little has changed. We still suspect flu when a high percentage of pigs have a sudden onset of barking cough, especially during temperature fluctuations in the fall or spring. However, the influenza viruses responsible for current flu outbreaks are quite different from past versions, and they represent a variable and dynamic population of viruses with increasing genetic diversity. This diversity confounds the ability to stimulate protective immunity through vaccine use and, perhaps, even through natural infection.

Prior to 1998, only one flu virus (now referred to as the classical H1N1 influenza virus) was responsible for seasonal outbreaks of swine flu. This flu was described as the sudden onset of coughing and respiratory distress that dissipated almost as quickly as it started. For roughly 80 years after the human pandemic influenza virus jumped to pigs around 1918, the H1N1 virus remained relatively stable in swine, and serologic studies suggested only sporadic and transient introductions of viruses of another subtype or from another species.

In 1998, a severe influenza-like disease surfaced almost simultaneously in pigs in North Carolina, Iowa, Minnesota and Texas. Causing these outbreaks was a new subtype introduced into swine from the human population; it was identified as influenza A viruses of the H3N2 subtype. Unlike the classical H1N1 virus, the H3N2 subtype was a triple reassortant. This means that it contained a mixture of gene segments derived from influenza viruses from swine, human and avian species. The triple-reassortant virus quickly became endemic in U.S. swine due to a lack of immunity in the pig population as well as the H3N2 virus" successful adaptation to the swine host. By the end of 1999, the H3N2 virus was detected throughout the Midwest, and once established, it didn't take long before other variant influenza viruses began to emerge due to viral reassortment between the H3N2 and classical H1N1 viruses. Although the H3N2 virus is currently endemic in North American swine, its introduction had a significant impact on the current and future variation of influenza viruses in pigs. There are now three subtypes of swine influenza viruses (H1N1, H3N2 and H1N2) that circulate in the swine population.

Influenza viruses have a unique genetic stucture that consists of eight different gene segments. This is unlike other swine viruses, such as porcine reproductive and respiratory syndrome virus, porcine circovirus or pseudorabies virus, which have linear non-segmented genomes. When two different subtypes of influenza virus infect the same pig (such as simultaneous infection with H1N1 and H3N2), gene segments can interchange between viruses through a process called viral reassortment. The influenza viruses that emerge after reassortment can pick up a different gene(s) and represent a new variant virus in the swine population that may not be completely cross-protected by immunity against the two original viruses. (See Figure 1.)

Influenza viral reassortment and the emergence of variant flu viruses in swine will certainly continue, and the resulting genetic and antigenic diversity may have multiple consequences for pork producers. Like humans, some species of birds and other mammals, swine have the potential to be infected with human- and avian-adapted influenza viruses, which have designated pigs as "mixing vessels" for influenza viruses from different species. The physiology of the hog's respiratory tract, along with the number of swine-adapted viruses endemic in swine populations around the world, may potentially increase the risk of viral reassortment between human, avian and swine influenza viruses. The human 2009 pandemic H1N1 influenza virus was a reassortant virus from multiple genetic lineages that became infamously known as "swine flu" due to the suggested origin of the virus in swine. The pandemic H1N1 virus is now endemic in swine worldwide due to human movement and subsequent transmission to pigs.

This is a major reason why it's important that swine workers receive flu vaccinations to prevent human-to-swine transmission.

Producers also should be aware that current influenza vaccines used in swine may not protect against new variant viruses that emerge due to viral reassortment or through the gradual change or antigenic drift of a resident virus. Although commercial inactivated vaccines contain multiple strains, representing viruses currently circulating in swine, it's difficult for biological companies to change vaccines as often as the virus changes in the swine population or to cover all existing antigenic variants possible in the United States. This has encouraged the use of autogenous vaccines made from viruses specific to a farm and under the herd veterinarian's recommendation. However, autogenous vaccines are subject to the same potential lack of cross-protection that can occur when a herd is exposed to new or multiple viruses. Thus, mismatching between the vaccine strain and the strain currently infecting a group of pigs may remain a common occurrence. When it appears that a vaccine is no longer preventing influenza infection in a herd, genetic sequencing will help determine if a new flu strain is present and predict if the vaccine is able to cross-protect.

It's not known why it took over 80 years before new influenza subtypes emerged and were consistently detected in U.S. swine. These viruses may have been present but remained undetected due to more primitive detection methods and genetic analysis at that time. However, there were sporadic reports of reassortant viruses in pigs before 1998 that were unable to sustain sufficient pig-to-pig transmission to become endemic. Viruses circulating between 1998 and 2009 in U.S swine were all triple-reassortant viruses with a similar set of swine, human and avian lineage gene segments. It's possible this particular combination of genes allowed influenza viruses to maintain a high transmission level, co-circulation of diverse genetic variants and reassortment to become successful in the swine population and, combined with modern production practices, may have led to a "perfect storm." We can only speculate why virus diversity rapidly increased in the last 13 years. (See Figure 2.)

Genetically and antigenically diverse influenza viruses will continue to emerge and this will have an impact on modern pork production and possibly human health. The potential emergence of a pandemic virus in swine with the ability to infect humans should remain a serious concern for the pork industry. However, industry consequences due to influenza virus detection in both the human and swine populations can be mitigated through monitoring and surveillance of emerging viruses in all susceptible species around the world, including swine. This requires engaging both human and animal health officials, researchers and diagnostic laboratories in a cooperative effort. Access to this information would be particularly valuable to veterinarians and pork producers through the development of efficacious influenza vaccines and changes in production practices if needed. The knowledge we gain has the ultimate goals of protecting the swine population from costly flu-related respiratory disease, protecting our industry from misinformation and protecting the human population our industry feeds.

Editor's note: Phil Gauger is a veterinar diagnostician at Iowa State University, and Amy Vincent is a veterinary medical office with USDA's Agricultural Research Service, National Animal Disease Center.