EPS8 Facilitates Uncoating of Influenza A Virus

[tetano]

Cell Rep. 2019 Nov 19;29(8):2175-2183.e4. doi: 10.1016/j.celrep.2019.10.064. EPS8 Facilitates Uncoating of Influenza A Virus.

Larson GP¹, Tran V¹, Y? S², Ca? Y², Higgins CA¹, Smith DM¹, Baker SF¹, Radoshitzky SR³, Kuhn JH², Mehle A⁴.
Author information

1 Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA. 2 Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, NIH, Frederick, MD 21702, USA. 3 Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. 4 Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: amehle@wisc.edu.

Abstract

All viruses balance interactions between cellular machinery co-opted to support replication and host factors deployed to halt the infection. We use gene correlation analysis to perform an unbiased screen for host factors involved in influenza A virus (FLUAV) infection. Our screen identifies the cellular factor epidermal growth factor receptor pathway substrate 8 (EPS8) as the highest confidence pro-viral candidate. Knockout and overexpression of EPS8 confirm its importance in enhancing FLUAV infection and titers. Loss of EPS8 does not affect virion attachment, uptake, or fusion. Rather, our data show that EPS8 specifically functions during virion uncoating. EPS8 physically associates with incoming virion components, and subsequent nuclear import of released ribonucleoprotein complexes is significantly delayed in the absence of EPS8. Our study identifies EPS8 as a host factor important for uncoating, a crucial step of FLUAV infection during which the interface between the virus and host is still being discovered.
Copyright ? 2019 The Author(s). Published by Elsevier Inc. All rights reserved.


KEYWORDS:

NCI-60; entry; epidermal growth factor receptor pathway substrate 8 (EPS8); gene correlation analysis; influenza virus; uncoating

PMID: 31747592 DOI: 10.1016/j.celrep.2019.10.064