Jul 21, 2016

S2 from Equine infectious anemia virus is an infectivity factor which counteracts the retroviral inhibitors SERINC5 and SERINC3

BioRxiv : the Preprint Server for Biology
Ajit ChandeMassimo Pizzato

Abstract

The lentivirus equine infectious anemia virus (EIAV) encodes S2, a pathogenic determinant important for virus replication and disease progression in horses. No molecular function has yet been linked to this accessory protein. We now report that S2 can replace the activity of Nef on HIV-1 infectivity, being required to antagonize the inhibitory activity of SERINC proteins on Nef-defective HIV-1. Similar to Nef, S2 excludes SERINC5 from virus particles and requires an ExxxLL motif predicted to recruit the clathrin adaptor AP2. Accordingly, a functional endocytic machinery is essential for S2-mediated infectivity enhancement, which is impaired by inhibitors of clathrin-mediated endocytosis. In addition to retargeting SERINC5 to a late endosomal compartment, S2 promotes the host factor degradation. Emphasizing the similarity with Nef, we show that S2 is myristoylated and, compatible with a crucial role of the post-translational modification, its N-terminal glycine is required for the anti-SERINC5 activity. EIAV-derived vectors devoid of S2 are less susceptible than HIV-1 to the inhibitory effect of both human and equine SERINC5. We then identified the envelope glycoprotein of EIAV as a determinant which also modulates retrovirus su...Continue Reading

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Mentioned in this Paper

Subfamily lentivirinae
Retrovir
Clathrin Adaptor
Virus
Post-Translational Protein Processing
Pathogenic Organism
Glycoproteins
Virion
Inhibitors
Virus Replication

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