Authors: Garten RJ, Davis CT, Russell CA et al. Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans. Sciencexpress 22 May 2009-05-25. http://www.sciencemag.org/cgi/content/abstract/1176225 and supporting material.(1,2)
Description (26th May 09)
In this article, a large group of authors predominantly from US laboratories report on a detailed analysis of the evolutionary history of the currently epidemic new Influenza A (H1N1)swl or swine origin 2009 A(H1N1) influenza viruses. In addition a group of viral isolates from the US and Mexico were antigenically analysed and their results reported.
Genetic structure of the new Influenza A (H1N1)-swl strain
From the beginning of the detection of the epidemic, it has been clear that the new strain known as A(H1N1)swl is a multiple reassortant, with gene segments derived from multiple previously described lineages. In this article, this finding is strongly supported by a phylogenetic (evolutionary history) analysis, in which the history of each of the virus 8 gene segments is described. This confirms the finding that the epidemic strain has appeared through a stepwise mixing of swine strains from North America (also called Classical swine strains), North American bird strains, Eurasian swine strains and Swine strains that have some time in the past acquired a gene from human influenza viruses. The process resulted in the “quadruple reassortant” new influenza A(H1N1) strain which has quickly spread in humans to and within a number of countries.
The genetic analysis also indicates that there are no immediate precursors among currently known swine influenza strains, probably since too few have been characterized. This suggests that the precursors may have circulated among swine for a long period of time before the zoonotic transmission to humans. Another finding is that all the new Influenza A (H1N1)-swl human strains are very similar, suggesting that they are all descendants of a recent, probably single transmission event from swine to human. It is currently not known where this event took place. Though another paper speculates this may be as late on as early in 2009.(3)
Somewhat surprisingly, genetic analysis of the US and Mexican strains failed to identify any mutations that in the past have been associated with adaptation to effective human-to-human transmission. This suggests that other, yet unknown genetic factors are responsible for this adaptation to human strains. The authors also report that the new Influenza A (H1N1)-swl strains are susceptible to oseltamivir and zanamivir and carry mutations known to confer resistance to adamantine antivirals.
In the study results from haemagglutination inhibition (HI) studies with ferret antisera are reported. The new Influenza A (H1N1)-swl viruses did not react with Ferret sera raised against currently circulating seasonal human A(H1N1) strains. This lack of cross reactivity suggests that immune experience of earlier seasonal A(H1N1) influenza would be unlikely to protect against the Influenza A (H1N1)-swl virus infection, although some minor protection cannot be completely ruled out. Other studies have suggested that only elderly individuals with possible exposure to influenza viruses in the 1950s might have some small protective immunity against the new A(H1N1)-swl strain.(3)
ECDC comment (26th May 2009)
This study convincingly shows that there is strong support for a probable origin in swine for the new A(H1N1)-swl strain. The virus has possibly been circulating in swine for some time before cross-species transmission to humans occurred. Of possible importance is that the virus contains antigenically important structural elements that are related to the original H1N1 viruses in birds that were the precursors to the 1918 pandemic, although they have evolved separately in swine for a long time. The authors make a case for increased surveillance for potential pandemic precursor viruses in swine which was advocated in Europe earlier this year.(4) While this would improve the potential for genetic analysis, there is no guarantee that all viruses with pandemic potential could be identified, especially as the authors themselves did not identify changes previously linked to adaptation to human transmission within new A(H1N1)-swl strain. Though it is reassuring that there are no known pathogenicity markers and only markers known to be associated with resistance to adamantanes (not to oseltamivir and zanamivir) this should not be seen as a permanent feature given the ability of influenza viruses to recombine and produce more threatening viruses.
1. Antigenic and Genetic Characteristics of Swine-Origin 2009 (H1N1) Influenza A Viruses Circulating in Humans. Garten, RJ et al. Sciencexpress 22 May 2009-05-25. http://www.sciencemag.org/cgi/content/abstract/1176225
2. Serum Cross-Reactive Antibody Response to a Novel Influenza A (H1N1) Virus After Vaccination with Seasonal Influenza Vaccine. MMWR, May 22, 2009 / 58(19);521-524. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5819a1.htm
3. Serum Cross-Reactive Antibody Response to a Novel Influenza A (H1N1) Virus After Vaccination with Seasonal Influenza Vaccine MMWR May 22, 2009 / 58(19);521-524 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5819a1.htm
4. Van Reeth K, Nicoll A A human case of swine influenza virus infection in Europe – implications for human health and research Eurosurveillance 2009 Volume 14, Issue 7, 19 February 2009; http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19124