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J Gen Virol. 2019 Feb;100(2):278-288. doi: 10.1099/jgv.0.001201. Epub 2018 Dec 19.

The antiviral activity of rodent and lagomorph SERINC3 and SERINC5 is counteracted by known viral antagonists.

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3​Institute of Medical Virology, University Hospital Frankfurt, Frankfurt, Germany.
1​CIBIO/InBIO- Research Network in Biodiversity and Evolutionary Biology, Campus de Vairão, University of Porto, Vairão, Portugal.
5​Institute of Virology, Technische Universität München/Helmholtz Zentrum, Munich, Germany.
4​Max von Pettenkofer Institute & Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, Germany.
2​Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal.
6​Gene Center and Department of Biochemistry, LMU München, Munich, Germany.
7​Department of Infectious Diseases, Integrative Virology, University Hospital Heidelberg, Heidelberg, Germany.
8​CITS - Centro de Investigação em Tecnologias de Saúde, CESPU, Gandra, Portugal.
9​University of Trento, Centre for Integrative Biology, Trento, Italy.


A first step towards the development of a human immunodeficiency virus (HIV) animal model has been the identification and surmounting of species-specific barriers encountered by HIV along its replication cycle in cells from small animals. Serine incorporator proteins 3 (SERINC3) and 5 (SERINC5) were recently identified as restriction factors that reduce HIV-1 infectivity. Here, we compared the antiviral activity of SERINC3 and SERINC5 among mice, rats and rabbits, and their susceptibility to viral counteraction to their human counterparts. In the absence of viral antagonists, rodent and lagomorph SERINC3 and SERINC5 displayed anti-HIV activity in a similar range to human controls. Vesicular stomatitis virus G protein (VSV-G) pseudotyped virions were considerably less sensitive to restriction by all SERINC3/5 orthologs. Interestingly, HIV-1 Nef, murine leukemia virus (MLV) GlycoGag and equine infectious anemia virus (EIAV) S2 counteracted the antiviral activity of all SERINC3/5 orthologs with similar efficiency. Our results demonstrate that the antiviral activity of SERINC3/5 proteins is conserved in rodents and rabbits, and can be overcome by all three previously reported viral antagonists.


HIV-1; SERINC; restriction factor; species-specific antagonism


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