Pandemic (H1N1) 2009 Virus Reassortment | CDC EID

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Volume 17, Number 2–February 2011
Research
Possible Increased Pathogenicity of Pandemic (H1N1) 2009 Influenza Virus upon Reassortment
Eefje J.A. Schrauwen, Sander Herfst, Salin Chutinimitkul, Theo M. Bestebroer, Guus F. Rimmelzwaan, Albert D.M.E. Osterhaus, Thijs Kuiken, and Ron A.M. Fouchier

Author affiliation: National Influenza Centre and Erasmus Medical Center Department of Virology, Rotterdam, the Netherlands

Suggested citation for this article

Abstract
Since emergence of the pandemic (H1N1) 2009 virus in April 2009, three influenza A viruses—seasonal (H3N2), seasonal (H1N1), and pandemic (H1N1) 2009—have circulated in humans. Genetic reassortment between these viruses could result in enhanced pathogenicity. We compared 4 reassortant viruses with favorable in vitro replication properties with the wild-type pandemic (H1N1) 2009 virus with respect to replication kinetics in vitro and pathogenicity and transmission in ferrets. Pandemic (H1N1) 2009 viruses containing basic polymerase 2 alone or in combination with acidic polymerase of seasonal (H1N1) virus were attenuated in ferrets. In contrast, pandemic (H1N1) 2009 with neuraminidase of seasonal (H3N2) virus resulted in increased virus replication and more severe pulmonary lesions. The data show that pandemic (H1N1) 2009 virus has the potential to reassort with seasonal influenza viruses, which may result in increased pathogenicity while it maintains the capacity of transmission through aerosols or respiratory droplets.

The influenza virus A (H1N1) that caused the first influenza pandemic of the 21st century, pandemic (H1N1) 2009, continues to be detected worldwide (1,2). The pandemic overall has been relatively mild; disease has ranged from subclinical infections to sporadic cases of severe pneumonia and acute respiratory distress syndrome (3–8). The virus responsible is a unique reassortant virus containing neuraminidase (NA) and matrix genes from the Eurasian swine influenza virus lineage, and the other 6 gene segments are derived from the North American triple reassortant swine influenza virus lineage (9). From the pandemic's start, there have been concerns the virus may mutate or reassort with contemporary influenza viruses and give rise to more pathogenic viruses.

Cocirculation of multiple strains of influenza virus A in humans provides an opportunity for viral genetic reassortment (mixing of genes from >2 viruses) (10). Genetic reassortment of pandemic (H1N1) 2009 virus with seasonal influenza A (H3N2) or seasonal influenza A (H1N1) viruses might thus represent a route to enhanced pathogenicity. No reassortment events between pandemic (H1N1) 2009 and seasonal viruses have been reported in humans. However, a triple-reassortant swine influenza virus A (H1N1), distinct from pandemic (H1N1) 2009 virus and containing the hemagglutinin (HA) and NA genes of seasonal influenza virus A (H1N1), was described recently (11). Dual infections by seasonal influenza A (H1N1) and seasonal influenza A (H3N2) viruses have been reported (12), as well as mixed infections of pandemic (H1N1) 2009 and seasonal influenza A (H3N2) viruses (13,14), highlighting the potential for reassortment of currently circulating influenza viruses. Subtype H1N2 reassortant influenza viruses that contain the HA of seasonal influenza A (H1N1) and the NA of seasonal influenza A (H3N2) viruses have been isolated from humans during previous influenza seasons, confirming that such HA/NA combinations can emerge in humans (15,16).

To investigate the potential for reassortment between seasonal influenza A and pandemic (H1N1) 2009 viruses, we used an in vitro selection method using reverse genetics and serial passaging under limited dilution conditions. Pathogenicity and transmission of these viruses were tested by using a ferret model. We report here the identification of 4 reassortants with different gene constellations.

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Pandemic (H1N1) 2009 Virus Reassortment | CDC EID



Suggested Citation for this Article
Schrauwen EJA, Herfst S, Chutinimitkul S, Bestebroer TM, Rimmelzwaan GF, Osterhaus ADME, et al. Possible increased pathogenicity of pandemic (H1N1) 2009 influenza virus upon reassortment. Emerg Infect Dis [serial on the Internet]. 2011 Feb [date cited]. http://www.cdc.gov/EID/content/17/2/200.htm


DOI: 10.3201/eid1702.101268


Comments to the Authors
Please use the form below to submit correspondence to the authors or contact them at the following address:

Ron A.M. Fouchier, Department of Virology, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, the Netherlands; email: r.fouchier@erasmusmc.nl