Transmission and pathogenicity of novel reassortants derived from Eurasian avian-like and 2009 pandemic H1N1 influenza viruses in mice and guinea pigs.

Weili Kong,Qiming He,Hanchun Yang,Yu Wang,Juan Pu,Kin-Chow Chang,Lirong Liu,Yuelong Shu,Zhihua Qin,Qinfang Liu,Honglei Sun,Yipeng Sun,Dayan Wang,Jinhua Liu,Xin Guo,Huijie Gao

doi:10.1038/srep27067

Abstract

Given the present extensive co-circulation in pigs of Eurasian avian-like (EA) swine H1N1 and 2009 pandemic (pdm/09) H1N1 viruses, reassortment between them is highly plausible but largely uncharacterized. Here, experimentally co-infected pigs with a representative EA virus and a pdm/09 virus yielded 55 novel reassortant viruses that could be categorized into 17 genotypes from Gt1 to Gt17 based on segment segregation. Majority of novel reassortants were isolated from the lower respiratory tract. Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs. The most transmissible reassortant genotypes demonstrated in guinea pigs (Gt2, Gt3, Gt7, Gt10 and Gt13) were also the most lethal in mice. Notably, nearly all these highly virulent reassortants (all except Gt13) were characterized with possession of EA H1 and full complement of pdm/09 ribonucleoprotein genes. Compositionally, we demonstrated that EA H1-222G contributed to virulence by its ability to bind avian-type sialic acid receptors, and that pdm/09 RNP conferred the most robust polymerase activity to reassortants. The present study revealed high reassortment compatibility between EA and pdm/09 viruses in pigs, which could give rise to progeny reassortant viruses with enhanced virulence and transmissibility in mice and guinea pig models.

Highlights

Restrictions[4,5,6]
To systematically examine reassortants obtained from co-infection of swine with EA and pdm/09 viruses, a representative EA virus A/Swine/Fujian/204/2007 (EA/FJ04) and a representative pdm/09 virus A/Beijing/7/2009 were selected for coinfection of six pigs inoculated by intranasal and intratracheal routes
A total of 300 purified viruses were isolated, of which 240 viruses were from nasal washes and 60 viruses were from bronchoalveolar fluids (BALFs)

Summary

Introduction

Restrictions[4,5,6]. EA H1N1 virus first emerged in Europe in 1979 and has replaced the classical swine H1N1 virus which indicates that the EA virus has competitive advantage in pigs[7,8,9]. Recent surveys of SIVs from 2009–2012 in South China found marked changes in the evolutionary patterns and ecosystem of SIVs and that only the internal genes of the pdm/09 virus were present in dominant lineages in pigs[10]. These observations suggest that reassortants between pdm/09 and EA H1N1 viruses could potentially generate reassortant viruses with novel antigenicity for humans. To better understand the genetic diversity and biological properties of novel reassortants between pdm/09 and EA influenza virus, we experimentally co-infected pigs with EA swine H1N1 and pdm/09 viruses, and examined the reassortant patterns of progeny viruses and their pathogenicity/transmissibility in mice and guinea pigs. We found that the two virus lineages could generate reassortant viruses with enhanced pathogenicity and transmissibility in both animal models, and that the most pathogenic and transmissible reassortants retained the EA H1 and full complement of pdm/09 RNP gene segments

Methods

Results

Conclusion