Mutations in the H7 HA and PB1 genes of avian influenza a viruses increase viral pathogenicity and contact transmission in guinea pigs

Carola Dreier,Patricia Resa-Infante,Swantje Thiele,Stephanie Stanelle-Bertram,Kerstin Walendy-Gnirß,Thomas Speiseder,Annette Preuss,Zacharias Müller,Hans-Dieter Klenk,Jürgen Stech,Gülsah Gabriel

doi:10.1080/22221751.2019.1663131

Abstract

ABSTRACT Avian influenza A viruses (AIV) of the H7 subtype continue to evolve posing a pandemic threat. However, molecular markers of H7N7 AIV pathogenicity and transmission in mammals remain poorly understood. In this study, we performed a systematic in vitro and in vivo analysis by comparing an H7N7 highly pathogenic AIV and its ferret adapted variant. Passaging an H7N7 AIV in ferrets led to six mutations in genes encoding the viral polymerase complex and the viral surface proteins. Here, we show that mutations in the H7 hemagglutinin gene cause increased pathogenicity in mice. Contact transmission between guinea pigs required additional mutations in the gene encoding the polymerase subunit PB1. Thus, particular vigilance is required with respect to HA and PB1 mutations as predictive molecular markers to assess the pandemic risk posed by emerging H7 avian influenza viruses.

Highlights

Emerging influenza A viruses (IAV) viruses continue to pose a major health burden
The SC35F virus obtained by serial lung-to-lung passages in ferrets, maintained its pathogenicity in chickens but became lethal in ferrets [11]
VCNA treated turkey red blood cells (TRBCs): TRBCs were treated with neuraminidase of Vibrio cholerae (VCNA) and the elimination of the sialic acids (SA) was assessed as a control. α2,3/α2,6 SA TRBCs: after VCNA treatment, the TRBCs were resialylated using either α2,6-sialyltransferase from Photobacterium damsela or α2,3-Sialyltransferase from Pasteurella multocida

Summary

Introduction

Emerging influenza A viruses (IAV) viruses continue to pose a major health burden. avian H5 and H7 IAV pose an ongoing threat for animal and human health. Until 2017, H7N9 IAV comprised of low pathogenic avian influenza viruses (LPAIV) only, causing no or little symptoms in poultry. H7N9 LPAIV managed to spread silently and widely in China to many administrative regions [6]. This silent nature of H7 LPAIV to cause subclinical disease in poultry made surveillance efforts challenging. In 2016, H7 LPAIV had evolved to a highly pathogenic avian influenza virus (H7 HPAIV) causing overt disease in humans and in poultry. Compared to its H7 LPAIV precursor, the H7 HPAIV was even able to spread to previously unaffected provinces in mainland China leading to large outbreaks in chicken farms and continuous infections in humans [6]. In contrast to the previous waves, the majority of circulating H7N9 strains in 2018 displayed the HPAIV phenotype [7]

Methods

Results

Conclusion