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

Vânia Passos (1, 2) , Thomas Zillinger (3) , Nicoletta Casartelli (4) , Amelie Wachs (5) , Shuting Xu (1) , Angelina Malassa (1) , Katja Steppich (1) , Hildegard Schilling (3) , Sergej Franz (1) , Daniel Todt (6) , Eike Steinmann (6) , Kathrin Sutter (7) , Ulf Dittmer (7) , Jens Bohne (5) , Olivier Schwartz (4) , Winfried Barchet (3, 8) , Christine Goffinet (1, 9, 10)

1 TWINCORE - Centre for Experimental and Clinical Infection Research [Hanover]
2 ICBAS - Instituto de Ciências Biomédicas de Abel Salazar
3 Institute of Clinical Chemistry and Clinical Pharmacology [Bonn, Allemagne]
4 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
5 MHH - Medizinische Hochschule Hannover = Hannover Medical School
6 RUB - Ruhr University Bochum = Ruhr-Universität Bochum
7 Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
8 DZIF - German Centre for Infection Research
9 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
10 BIH - Berlin Institute of Health

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.

Mots clés: CRISPR/Cas9; HIV-1; Nef; SERINC5; antiviral factor; human immunodeficiency virus; interferons

Domaines: Virologie

Vânia Passos, Thomas Zillinger, Nicoletta Casartelli, Amelie Wachs, Shuting Xu, et al.. Characterization of Endogenous SERINC5 Protein as Anti-HIV-1 Factor. Journal of Virology, 2019, 93 (24), pp.e01221-19. ⟨10.1128/JVI.01221-19⟩. ⟨pasteur-03253574⟩