Characterization of Endogenous SERINC5 Protein as Anti-HIV-1 Factor

Author:

Passos Vânia12,Zillinger Thomas3,Casartelli Nicoletta4,Wachs Amelie S.5,Xu Shuting1,Malassa Angelina1,Steppich Katja1,Schilling Hildegard3,Franz Sergej1,Todt Daniel6,Steinmann Eike6,Sutter Kathrin7,Dittmer Ulf7,Bohne Jens5,Schwartz Olivier4ORCID,Barchet Winfried38,Goffinet Christine1910ORCID

Affiliation:

1. Institute of Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, Hannover, Germany

2. Instituto de Ciências Biomédicas Abel Salazar, Universidade Do Porto, Porto, Portugal

3. Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital, University of Bonn, Bonn, Germany

4. Institut Pasteur, Department of Virology, Virus and Immunity Unit, Paris, France

5. Institute of Virology, Hannover Medical School, Hannover, Germany

6. Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany

7. Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

8. German Center for Infection Research (DZIF), Cologne-Bonn, Germany

9. Institute of Virology, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany

10. Berlin Institute of Health, Berlin, Germany

Abstract

SERINC5 is the long-searched-for antiviral factor that is counteracted by the HIV-1 accessory gene product Nef. Here, we engineered, via CRISPR/Cas9 technology, T-cell lines that express endogenous SERINC5 alleles tagged with a knocked-in HA epitope. This genetic modification enabled us to study basic properties of endogenous SERINC5 and to verify proposed mechanisms of HIV-1 Nef-mediated counteraction of SERINC5. Using this unique resource, we identified the susceptibility of endogenous SERINC5 protein to posttranslational modulation by type I IFNs and suggest uncoupling of Nef-mediated functional antagonism from SERINC5 exclusion from virions.

Funder

Bonfor

Berliner Institut für Gesundheitsforschung

Deutsche Forschungsgemeinschaft

Deutsches Zentrum für Infektionsforschung

Helmholtz Association

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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