A Historical Perspective of Influenza A(H1N2) Virus

Naomi Komadina

, Jodie McVernon, Robert Hall, and Karin Leder

Author affiliations: World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria, Australia. (N. Komadina); Monash University, Melbourne (N. Komadina, R. Hall, K. Leder); The University of Melbourne, Melbourne (J. McVernon); Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia (J. McVernon);Victorian Infectious Diseases Services, Melbourne (K. Leder)

Abstract

The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals.

During 2009, emergence of influenza A(H1N1)pdm09 as a pandemic virus heightened public awareness of the potential for human influenza viruses to mutate. The viruses had been transmitted to animal reservoirs decades earlier, evolved, and were reintroduced to human populations as novel reassortant viruses (1). Reinforcing this concept, during 2012, >300 human cases of swine-origin influenza A(H3N2) variant (v) viruses were reported in the United States, predominantly acquired through close contact with pigs at agricultural shows, leading to 11 hospitalizations. The virus had limited person-to-person spread during 2012; a seed vaccine virus was developed for response to the H3N2v strain should the virus become readily transmissible among humans (2).

A swine-origin influenza subtype variant, A(H1N2)v, which was lesser known than H3N2v, infected 4 persons attending agricultural shows during the final days of the agricultural show season (3). Late emergence of this virus may have limited its spread. Although there was no evidence of human-to-human transmission, there was concern that the presence of the matrix protein derived from the A(H1N1)pdm09 virus, which had been circulating widely in the human population since 2009, could potentially confer the A(H1N2)v virus with increased transmissibility among humans (3).

Novel influenza viruses can arise among humans either by direct transmission from mammalian or avian sources or through genetic reassortment. The segmented nature of the influenza viral genome allows reassortment to occur in a host that is simultaneously infected with >2 subtypes of influenza A viruses. Although influenza viruses exhibit some host specificity, swine are susceptible to infection with viruses of avian and mammalian lineages, facilitated by the presence of receptors for both lineages in the respiratory tract. Swine can therefore serve as “mixing vessels” for different lineages, providing an opportunity for novel reassortants to arise. The reassortant viruses may acquire mammalian adaption characteristics, thereby allowing infection of humans to occur (4).

A(H1N2) viruses have been described among avian, swine, and human populations. Like A(H3N2) and A(H1N1) viruses, A(H1N2) viruses have become established in swine herds in many regions. In contrast, A(H3N2) and A(H1N1)pdm09 were the only type A viruses documented as circulating among humans as of 2009. Worldwide, 1 case of a human-origin reassortant was reported between 2003 and the events of 2012 in the United States (5). Here, we document the distinct lineages of swine and human influenza H1N2 subtypes, cross-species reassortment, and transmission events that result in the emergence of novel viruses.