Publication Date:
2015-09-30
Description:
HIV-1 Nef, a protein important for the development of AIDS, has well-characterized effects on host membrane trafficking and receptor downregulation. By an unidentified mechanism, Nef increases the intrinsic infectivity of HIV-1 virions in a host-cell-dependent manner. Here we identify the host transmembrane protein SERINC5, and to a lesser extent SERINC3, as a potent inhibitor of HIV-1 particle infectivity that is counteracted by Nef. SERINC5 localizes to the plasma membrane, where it is efficiently incorporated into budding HIV-1 virions and impairs subsequent virion penetration of susceptible target cells. Nef redirects SERINC5 to a Rab7-positive endosomal compartment and thereby excludes it from HIV-1 particles. The ability to counteract SERINC5 was conserved in Nef encoded by diverse primate immunodeficiency viruses, as well as in the structurally unrelated glycosylated Gag from murine leukaemia virus. These examples of functional conservation and convergent evolution emphasize the fundamental importance of SERINC5 as a potent anti-retroviral factor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosa, Annachiara -- Chande, Ajit -- Ziglio, Serena -- De Sanctis, Veronica -- Bertorelli, Roberto -- Goh, Shih Lin -- McCauley, Sean M -- Nowosielska, Anetta -- Antonarakis, Stylianos E -- Luban, Jeremy -- Santoni, Federico Andrea -- Pizzato, Massimo -- DP1DA034990/DA/NIDA NIH HHS/ -- England -- Nature. 2015 Oct 8;526(7572):212-7. doi: 10.1038/nature15399. Epub 2015 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Trento, Centre for Integrative Biology, 38123 Trento, Italy. ; University of Trento, Laboratory of Biomolecular Sequence and Structure Analysis for Health, NGS facility, 38123 Trento, Italy. ; University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, Massachusetts 01605, USA. ; University of Geneva, Department of Genetic Medicine and Development, Geneva 1211, Switzerland. ; iGE3 Institute of Genetics and Genomics of Geneva, Geneva 1211, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26416734" target="_blank"〉PubMed〈/a〉
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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