The 2009 H1N1 virus causing the current “swine” Flu
In 1918, H1N1 influenza viruses caused a pandemic in humans. This virus has continued to circulate in humans since 1918 until today, with a gap from 1957 to 1977. Today, H1N1 viruses are derived but different from the 1918 virus, due to extensive drifting of the virus in the human population for more than 70 years.
In 1918, H1N1 influenza viruses also caused a pandemic in pigs. The swine 1918 virus was very similar to the human 1918 virus, and they share a common ancestor. Since 1918, H1N1 virus established a swine lineage independent of the human lineage, and they drifted in pigs for more than 90 years. These swine H1N1 viruses are named “classical swine H1N1” to distinguish them from other more recent swine viruses that have also been affecting the pig population more recently. The current classical H1N1 swine viruses are derived but different from the 1918 virus, also due to drifting, but since the swine lineage has been independent of the human lineage, these swine H1N1 are different from the human H1N1s.
From 1918 to 1997, there have been no major surprises among swine influenza viruses in the Americas. While humans experienced two pandemics, H2 and H3 pandemics, there were no changes in the subtypes of influenza viruses circulating in pigs, which remained classical H1N1 viruses. However, in 1997, thing changed for pigs. Many different new influenza virus genotypes emerged, and a particular one became prevalent and started to co-circulate with the classical H1N1 viruses. This was a triple reassortant virus, with genes derived from classical swine (NP, M and NS), genes from avian influenza viruses (PB2 and PA) and genes from a human H3N2 virus (H3N2). These H3N2 viruses have been circulating in pigs since 1997 and established an independent lineage from the human H3N2s. In addition, these viruses have continued to reassort with classical H1N1 viruses in the pig population, so different genotypes have been established in swine since 1997.
The virus that has caused the current outbreak is one of these swine reassortants. It contains the H1 from classical swine, and some other genes derived from swine, avian and human viruses coming from the H3N2 triple reassortant. In addition, it contains also some genes from the Eurasian lineage of swine influenza viruses, and it is unclear how Eurasian swine viruses have arrived to the Americas and reassorted with the American swine lineages.
The current outbreak indicates that the new H1N1 viruses are able to transmit from human to human, and this distinguishes these viruses form other viruses present in nature. There are able to do so even in an unusual season for influenza virus outbreaks. Transmission of influenza virus is more efficient in winter times, and this determines the seasonality of the yearly influenza epidemics. Only during pandemic times, there has been an interwinter wave of influenza virus epidemics. Since these H1s come from a swine lineage, the antigenic differences between the HA of these viruses and the HA of the human H1N1 viruses circulating the last winter season are much more than what one expect during the usual yearly drift, making imperative the use of a vaccine based on these new H1N1s were they become prevalent in the next winter. However, at this moment it cannot be excluded that this virus will die off in humans, and whether previous human viruses H1N1 and H3N2 will still be circulating next winter, so the possibility of adding a new vaccine component based on this new H1N1 to the current trivalent vaccine needs also to be considered.
The new H1N1 virus is sensitive to neuraminidase inhibitors, and while existing vaccines are unlikely to provide protection against infection, natural immunity against previously circulating H1N1 viruses might temper the potential of this virus to cause severe disease in humans. It is also not possible to predict whether the virulence of the virus will change as it continues to propagate in humans, but most of the data indicate that the virus is not especially more virulent in humans than previously circulating viruses. The apparent high death rate in Mexico might be a consequence of a high number of mild infections that might have not been diagnosed
Professor, Department of Microbiology
Fischberg Professor, Department of Medicine, Division of Infectious Diseases
Co-Director, Global Health and Emerging Pathogens Institute
Mount Sinai School of Medicine
1 Gustave L. Levy Place
New York, NY 1002