Reassortment between Avian H5N1 and Human Influenza Viruses Is Mainly Restricted to the Matrix and Neuraminidase Gene Segments

Eefje J A Schrauwen,Ron A M Fouchier,Theo M Bestebroer,Sander Herfst,Guus F Rimmelzwaan,Albert D M E Osterhaus,Gourapura J Renukaradhya

doi:10.1371/journal.pone.0059889

Eefje J A Schrauwen, Ron A M Fouchier + Show 5 more

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https://doi.org/10.1371/journal.pone.0059889

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Journal: PloS one	Publication Date: Mar 20, 2013
Citations: 59	License type: CC BY 4.0

Affiliation: Erasmus University Rotterdam

Abstract

Highly pathogenic avian influenza H5N1 viruses have devastated the poultry industry in many countries of the eastern hemisphere. Occasionally H5N1 viruses cross the species barrier and infect humans, sometimes with a severe clinical outcome. When this happens, there is a chance of reassortment between H5N1 and human influenza viruses. To assess the potential of H5N1 viruses to reassort with contemporary human influenza viruses (H1N1, H3N2 and pandemic H1N1), we used an in vitro selection method to generate reassortant viruses, that contained the H5 hemagglutinin gene, and that have a replication advantage in vitro. We found that the neuraminidase and matrix gene segments of human influenza viruses were preferentially selected by H5 viruses. However, these H5 reassortant viruses did not show a marked increase in replication in MDCK cells and human bronchial epithelial cells. In ferrets, inoculation with a mixture of H5N1-pandemic H1N1 reassortant viruses resulted in outgrowth of reassortant H5 viruses that had incorporated the neuraminidase and matrix gene segment of pandemic 2009 H1N1. This virus was not transmitted via aerosols or respiratory droplets to naïve recipient ferrets. Altogether, these data emphasize the potential of avian H5N1 viruses to reassort with contemporary human influenza viruses. The neuraminidase and matrix gene segments of human influenza viruses showed the highest genetic compatibility with HPAI H5N1 virus.

Highlights

Since the late 1990s, highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype have devastated the poultry industry of numerous countries of the eastern hemisphere
Upon H5N1-pandemic H1N1 (pH1N1) transfection and passaging of the virus mixtures, wild type H5N1 was recovered in one attempt and H5N1-pH1N1-reassortants in three attempts (Table 2)
At least two human influenza pandemics in the last century were linked to lineages where circulating human influenza viruses reassorted with influenza genes of non-human origin [9]

Summary

Introduction

Since the late 1990s, highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype have devastated the poultry industry of numerous countries of the eastern hemisphere. HPAI H5N1 viruses cross the species barrier and infect humans, sometimes with a severe clinical outcome. This direct transmission of HPAI H5N1 virus to humans was first detected in 1997 [1] and has continued to be reported ever since [2]. These viruses do not transmit efficiently between humans. They may gain the ability to spread efficiently among humans through either virus adaptation to the new host, genetic reassortment (ie genetic mixing of viruses) with contemporary human influenza viruses, or both [3,4,5,6]. The influenza pandemics of 1957, 1968 and 2009 were the result of reassortment events [7,8,9]

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