The Endonucleolytic RNA Cleavage Function of nsp1 of Middle East Respiratory Syndrome Coronavirus Promotes the Production of Infectious Virus Particles in Specific Human Cell Lines

Author:

Nakagawa Keisuke1,Narayanan Krishna1,Wada Masami1,Popov Vsevolod L.2,Cajimat Maria2,Baric Ralph S.3,Makino Shinji14567

Affiliation:

1. Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA

2. Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA

3. Department of Epidemiology and Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

4. Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston, Texas, USA

5. UTMB Center for Tropical Diseases, The University of Texas Medical Branch, Galveston, Texas, USA

6. Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, Texas, USA

7. Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, USA

Abstract

MERS-CoV represents a high public health threat. Because CoV nsp1 is a major viral virulence factor, uncovering the biological functions of MERS-CoV nsp1 could contribute to our understanding of MERS-CoV pathogenicity and spur development of medical countermeasures. Expressed MERS-CoV nsp1 suppresses host gene expression, but its biological functions for virus replication and effects on host gene expression in infected cells are largely unexplored. We found that nsp1 suppressed host gene expression in infected cells. Our data further demonstrated that nsp1, which was not detected in virus particles, promoted virus assembly or budding in a 293-derived cell line, leading to efficient virus replication. These data suggest that nsp1 plays an important role in MERS-CoV replication and possibly affects virus-induced diseases by promoting virus particle production in infected hosts. Our data, which uncovered an unexpected novel biological function of nsp1 in virus replication, contribute to further understanding of the MERS-CoV replication strategies.

Funder

HHS | National Institutes of Health

University of Texas Medical Branch

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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