Viral and Host Factors Required for Avian H5N1 Influenza A Virus Replication in Mammalian Cells

Hong Zhang,Benjamin Hale,Ke Xu,Bing Sun

doi:10.3390/v5061431

Abstract

Following the initial and sporadic emergence into humans of highly pathogenic avian H5N1 influenza A viruses in Hong Kong in 1997, we have come to realize the potential for avian influenza A viruses to be transmitted directly from birds to humans. Understanding the basic viral and cellular mechanisms that contribute to infection of mammalian species with avian influenza viruses is essential for developing prevention and control measures against possible future human pandemics. Multiple physical and functional cellular barriers can restrict influenza A virus infection in a new host species, including the cell membrane, the nuclear envelope, the nuclear environment, and innate antiviral responses. In this review, we summarize current knowledge on viral and host factors required for avian H5N1 influenza A viruses to successfully establish infections in mammalian cells. We focus on the molecular mechanisms underpinning mammalian host restrictions, as well as the adaptive mutations that are necessary for an avian influenza virus to overcome them. It is likely that many more viral and host determinants remain to be discovered, and future research in this area should provide novel and translational insights into the biology of influenza virus-host interactions.

Highlights

Influenza viruses are enveloped viruses containing a segmented negative-sense RNA genome, and belong to the Orthomyxoviridae family [1]
We summarize known viral and host-cell factors implicated in allowing avian H5N1 influenza viruses to establish successful infections in mammalian cells, and briefly discuss adaptive mutations in the viral genome that may be necessary to allow this to occur
We have summarized current knowledge pertaining to molecular mechanisms involved in efficient mammalian infection by avian H5N1 influenza A viruses

Summary

Introduction

Influenza viruses are enveloped viruses containing a segmented negative-sense RNA genome, and belong to the Orthomyxoviridae family [1]. Considering the existence of a large avian influenza virus gene pool, and the frequent interspecies transmission of viruses between birds and mammalian species, it is possible that more subtypes will establish themselves as future mammalian influenza viruses. Transcription, and protein synthesis, NEP (nuclear export protein), and M1, act to traffic newly synthesized vRNPs out of the nucleus, into the cytoplasm, and to the plasma membrane, where assembly of progeny virions occurs At these sites, several viral proteins contribute to budding, including M1 and M2. We summarize known viral and host-cell factors implicated in allowing avian H5N1 influenza viruses to establish successful infections in mammalian cells, and briefly discuss adaptive mutations in the viral genome that may be necessary to allow this to occur. Molecular Mechanisms of Avian H5N1 Influenza A Virus Replication in Mammalian Cells

Crossing the Plasma Membrane

Replication in the Nucleus

Escaping the Host Immune Response

Release from the Cell Surface

Findings

Summary