Eurasian Avian-like M1 Plays More Important Role than M2 in Pathogenicity of 2009 Pandemic H1N1 Influenza Virus in Mice.

Lixiang Xie,Lingxiang Xin,Rujuan Wu,Zhaofei Wang,Mingqing Wu,Hengan Wang,Yuqiang Cheng,Jingjiao Ma,Jianhe Sun,Guanlong Xu,Yaxian Yan

doi:10.3390/v13122335

Abstract

Reassortant variant viruses generated between 2009 H1N1 pandemic influenza virus [A(H1N1)pdm09] and endemic swine influenza viruses posed a potential risk to humans. Surprisingly, genetic analysis showed that almost all of these variant viruses contained the M segment from A(H1N1)pdm09, which originated from Eurasian avian-like swine influenza viruses. Studies have shown that the A(H1N1)pdm09 M gene is critical for the transmissibility and pathogenicity of the variant viruses. However, the M gene encodes two proteins, M1 and M2, and which of those plays a more important role in virus pathogenicity remains unknown. In this study, the M1 and M2 genes of A(H1N1)pdm09 were replaced with those of endemic H3N2 swine influenza virus, respectively. The chimeric viruses were rescued and evaluated in vitro and in mice. Both M1 and M2 of H3N2 affected the virus replication in vitro. In mice, the introduction of H3N2 M1 attenuated the chimeric virus, where all the mice survived from the infection, compared with the wild type virus that caused 100 % mortality. However, the chimeric virus containing H3N2 M2 was still virulent to mice, and caused 16.6% mortality, as well as similar body weight loss to the wild type virus infected group. Compared with the wild type virus, the chimeric virus containing H3N2 M1 induced lower levels of inflammatory cytokines and higher levels of anti-inflammatory cytokines, whereas the chimeric virus containing H3N2 M2 induced substantial pro-inflammatory responses, but higher levels of anti-inflammatory cytokines. The study demonstrated that Eurasian avian-like M1 played a more important role than M2 in the pathogenicity of A(H1N1)pdm09 in mice.

Highlights

A swine-origin H1N1 influenza virus, first reported in Mexico in April 2009, resulted in human infection, and became widespread
All the results demonstrated that both Matrix protein 1 (M1) and matrix protein 2 (M2) contribute to the virulence of CA09, whereas the CA09 M1 plays a more critical role than M2 in the pathogenicity of CA09 in mice
A study showed that the corporation of Eurasian avian-like NA and M genes is critical for the pathogenicity of A(H1N1)pdm09 [45]

Summary

Introduction

A swine-origin H1N1 influenza virus, first reported in Mexico in April 2009, resulted in human infection, and became widespread. The A(H1N1)pdm infection was confirmed with 180,000 cases reported globally [1]. The influenza human infection cases of A(H1N1)pdm were more predominant in the 2009/2010 season than human seasonal H1N1 and H3N2 subtypes, and caused high mortality rates [2,3]. The gene analysis confirmed this virus to be a reassortant virus with six genes (PB2, PB1, PA, HA, NP, and NS) from North American triple-reassortant influenza viruses, and two genes (M, NA) from Eurasian avian-like swine influenza viruses [4]. Pigs are considered to be “mixing vessels” because they have receptors for both avian- and human-like influenza viruses. H3N2 M1 or H3N2 M2 attenuated the chimeric viruses compared with the wild type virus. Mortality in mice, and a similar body weight loss to the wild type virus infected group. All the results suggested that the Eurasian avian-like M1 played a more important role than

Methods

Results

Conclusion