Strain-Specific Antagonism of the Human H1N1 Influenza A Virus against Equine Tetherin.

Meiyue Wang,Zhenyu Zhang,Xiaojun Wang

doi:10.3390/v10050264

Meiyue Wang, Zhenyu Zhang + Show 1 more

Open Access

https://doi.org/10.3390/v10050264

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Abstract

Tetherin/BST-2/CD317 is an interferon-induced host restriction factor that can block the budding of enveloped viruses by tethering them to the cell surface. Many viruses use certain proteins to counteract restriction by tetherin from their natural hosts, but not from other species. The influenza A virus (FLUAV) has a wide range of subtypes with different host tropisms. Human tetherin (huTHN) has been reported to restrict only specific FLUAV strains and the viral hemagglutinin (HA) and neuraminidase (NA) genes determine the sensitivity to huTHN. Whether tetherins from other hosts can block human FLUAV is still unknown. Here, we evaluate the impact of equine tetherin (eqTHN) and huTHN on the replication of A/Sichuan/1/2009 (H1N1) and A/equine/Xinjiang/1/2007 (H3N8) strains. Our results show that eqTHN had higher restriction activity towards both viruses, and its shorter cytoplasmic tail contributed to that activity. We further demonstrated that HA and NA of A/Hamburg/4/2009 (H1N1) could counteract eqTHN. Notably, our results indicate that four amino acids, 13T and 49L of HA and 32T and 80V of NA, were involved in blocking the restriction activity of eqTHN. These findings reveal interspecies restriction by eqTHN towards FLUAV, and the role of the HA and NA proteins in overcoming this restriction.

Highlights

Viruses and their hosts undergo coevolution and adaptation over long time scales and most viruses have a defined range of hosts
We find that equine tetherin (eqTHN), but not Human tetherin (huTHN), has restriction activity towards human FLUAV A/Sichuan/1/2009 (H1N1) and equine FLUAV A/equine/Xinjiang/1/2007 (H3N8)
We first addressed whether huTHN and eqTHN proteins exerted an influence on FLUAV release

Summary

Introduction

Viruses and their hosts undergo coevolution and adaptation over long time scales and most viruses have a defined range of hosts. Most retroviruses have strict host tropism and can rarely jump from one species to another. To successfully replicate in host cells, viruses need to counteract various host restriction factors at different replication steps. It is evident from several reports that host restriction factors, such as apolipoprotein B mRNA-editing enzyme catalytic subunit 3 proteins (APOBEC3) [3,4,5], tripartite motif protein 5a (TRIM5a) [6], SAM domain and HD domain-containing protein 1 (SAMHD1) [7,8], and tetherin [9] play important roles in blocking interspecies transmission of retroviruses. As with several other restriction factors, like interferon-induced transmembrane proteins (IFITMs), tetherin has been shown to have broad antiviral activity against different enveloped viruses from various virus families including human immunodeficiency virus 1 (HIV-1), Ebola virus and human herpes virus 8 (HHV8) [10,11,12]

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