Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus

PLoS Pathogens

Sina Bavari¹  I-Chueh Huang²  Jessica J. Chiang²  Charles C. Bailey²  Jessica L. Weyer²  Asim A. Ahmed³  Michael Farzan³  Hyeryun Choe⁴  Michelle M. Becker⁴  Jens H. Kuhn⁵  Abraham L. Brass⁶  Stephen J. Elledge⁷  Dutch Boltz⁸  Sheli R. Radoshitzky⁸  Mark R. Denison⁸  Xiaoli Chi⁸  Lian Dong⁸  Lindsay E. Longobardi⁸ 

[1] Department of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, United States of America;Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts, United States of America;Department of Pediatrics, Harvard Medical School, Children's Hospital, Boston, Massachusetts, United States of America;Departments of Pediatrics and Microbiology and Immunology and Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America;Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, National Interagency Biodefense Campus, Frederick, Maryland, United States of America;Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Charlestown, Massachusetts, United States of America;Tunnell Consulting Inc., King of Prussia, Pennsylvania, United States of America;US Army Medical Research Institute of Infectious Disease, National Interagency Biodefense Campus, Frederick, Maryland, United States of America

关键词: Influenza A virus;    SARS coronavirus;    Protein expression;    Virions;    Membrane proteins;    Vector-borne diseases;    Ebola virus;    Lysosomes;   

DOI  :  10.1371/journal.ppat.1001258

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP1,2) of Marburg and Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV) and entry mediated by the SARS-CoV spike (S) protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.

【 授权许可】

CC BY