The gene-edited Jurkat clone P1E8, labelled with Cell TrackerTM Red CMTPX Dye and immunostained with anti-HA (red fluorescence, shows endogenous SERINC5). PFA-fixed were analyzed by confocal microscopy.

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08.10.2019

New insights into the anti HIV-1 restriction factor SERINC5

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The research group of Christine Goffinet established new properties of the antiviral restriction factor SERINC5. Restriction factors are proteins of the cell-intrinsic innate immune system that interfere with virus replication. However, several viruses have evolved strategies to evade or counteract these cellular defenses. The transmembrane protein SERINC5 incorporates into and reduces the infectivity of HIV-1 particles and is antagonized by the HIV-1 accessory protein Nef. Because antibodies of sufficient sensitivity and specificity against SERINC5 do not exist, studies addressing the subcellular localization and properties as anti-HIV-1 restriction factors were largely restricted to heterologously expressed protein. Here, an HA epitope tag was inserted into the SERINC5 gene alleles of a T-cell line via CRISP/Cas9-assisted gene editing. This modification allowed, for the first time, the detection of endogenously expressed SERINC5 protein. This unique tool allowed deciphering an unexpected modulation of subcellular localization of SERINC5 protein through type I interferons and identifying Nef-mediated antagonism modes that go beyond the so far suggested Nef-mediated virion exclusion of SERINC5. CRISPR/Cas9-mediated gene editing paves avenues towards understanding of the impact of single nucleotide polymorphisms in genes encoding antiviral factors, an important step towards personalized medicine. This project is funded by the Collaborative Research Centre 900 (Sonderforschungsbereich 900) “Microbial Persistence and its Control” of the German Research Foundation.

Characterization of Endogenous SERINC5 Protein as anti-HIV-1 Factor, Vânia Passos, Thomas Zillinger, Nicoletta Casartelli, Amelie S. Wachs, Shuting Xu, Angelina Malassa, Katja Steppich, Hildegard Schilling, Sergej Franz, Daniel Todt, Eike Steinmann, Kathrin Sutter, Ulf Dittmer, Jens Bohne, Olivier Schwartz, Winfried Barchet, and Christine Goffinet, Journal of Virology 2019, Epub ahead of print

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Link to the open access article: https://jvi.asm.org/content/early/2019/10/03/JVI.01221-19

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