Reduced Replication of Highly Pathogenic Avian Influenza Virus in Duck Endothelial Cells Compared to Chicken Endothelial Cells Is Associated with Stronger Antiviral Responses.

Anja De Bruin,Mathilde Richard,Ron Fouchier,Monique Spronken,Theo Bestebroer

doi:10.3390/v14010165

Abstract

Highly pathogenic avian influenza viruses (HPAIVs) cause fatal systemic infections in chickens, which are associated with endotheliotropism. HPAIV infections in wild birds are generally milder and not endotheliotropic. Here, we aimed to elucidate the species-specific endotheliotropism of HPAIVs using primary chicken and duck aortic endothelial cells (chAEC and dAEC respectively). Viral replication kinetics and host responses were assessed in chAEC and dAEC upon inoculation with HPAIV H5N1 and compared to embryonic fibroblasts. Although dAEC were susceptible to HPAIV upon inoculation at high multiplicity of infection, HPAIV replicated to lower levels in dAEC than chAEC during multi-cycle replication. The susceptibility of duck embryonic endothelial cells to HPAIV was confirmed in embryos. Innate immune responses upon HPAIV inoculation differed between chAEC, dAEC, and embryonic fibroblasts. Expression of the pro-inflammatory cytokine IL8 increased in chicken cells but decreased in dAEC. Contrastingly, the induction of antiviral responses was stronger in dAEC than in chAEC, and chicken and duck fibroblasts. Taken together, these data demonstrate that although duck endothelial cells are permissive to HPAIV infection, they display markedly different innate immune responses than chAEC and embryonic fibroblasts. These differences may contribute to the species-dependent differences in endotheliotropism and consequently HPAIV pathogenesis.

Highlights

Avian influenza A viruses (AIVs) are maintained through enzootic circulation in wild waterfowl, predominantly in the orders of the Anseriformes and Charadriiformes [1]
We aimed to mimic the apical infection of endothelial cells following systemic dissemination of highly pathogenic avian influenza viruses (HPAIVs) in vivo
We show that primary duck endothelial cells are susceptible to A/Vietnam/1203/04 and reverse genetics (RG)-A/turkey/Turkey/1/05, two H5N1 HPAIVs that cause severe disease in young Pekin ducks yet without endotheliotropism [75,76], upon direct inoculation in vitro and in ovo

Summary

Introduction

Avian influenza A viruses (AIVs) are maintained through enzootic circulation in wild waterfowl, predominantly in the orders of the Anseriformes (e.g., ducks, geese, and swans) and Charadriiformes (e.g., gulls) [1]. Infections with influenza viruses in wild waterfowl are mostly asymptomatic and do not cause histological lesions [3,4]. In these species, AIV tropism is limited to the digestive tract [5]. AIVs can be of low pathogenicity causing mild or subclinical disease in the respiratory and gastrointestinal tracts [7]. These viruses were coined low-pathogenic avian influenza viruses (LPAIVs). Viruses of the H5 and H7 subtypes can mutate into highly pathogenic avian influenza viruses (HPAIVs) in terrestrial poultry, leading to severe systemic infections with mortality rates reaching 100% [7]

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