title: HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation.
abstract: 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.
authors.affiliation: University of Trento, Centre for Integrative Biology, 38123 Trento, Italy.
authors.forename: Annachiara
authors.initials: A
authors.lastname: Rosa
authors.affiliation: University of Trento, Centre for Integrative Biology, 38123 Trento, Italy.
authors.forename: Ajit
authors.initials: A
authors.lastname: Chande
authors.affiliation: University of Trento, Centre for Integrative Biology, 38123 Trento, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Ziglio
authors.affiliation: University of Trento, Laboratory of Biomolecular Sequence and Structure Analysis for Health, NGS facility, 38123 Trento, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: De Sanctis
authors.affiliation: University of Trento, Laboratory of Biomolecular Sequence and Structure Analysis for Health, NGS facility, 38123 Trento, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bertorelli
authors.affiliation: University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, Massachusetts 01605, USA.
authors.forename: Shih Lin
authors.initials: SL
authors.lastname: Goh
authors.affiliation: University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, Massachusetts 01605, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: McCauley
authors.affiliation: University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, Massachusetts 01605, USA.
authors.forename: Anetta
authors.initials: A
authors.lastname: Nowosielska
authors.affiliation: University of Geneva, Department of Genetic Medicine and Development, Geneva 1211, Switzerland.|iGE3 Institute of Genetics and Genomics of Geneva, Geneva 1211, Switzerland.
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.affiliation: University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, Massachusetts 01605, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Luban
authors.affiliation: University of Geneva, Department of Genetic Medicine and Development, Geneva 1211, Switzerland.
authors.forename: Federico Andrea
authors.initials: FA
authors.lastname: Santoni
authors.affiliation: University of Trento, Centre for Integrative Biology, 38123 Trento, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pizzato
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D019143:Evolution, Molecular; D015683:Gene Products, gag / Q000378:metabolism; D015693:Gene Products, nef / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000502:physiology*; D058507:Host Specificity; D054884:Host-Pathogen Interactions; D006801:Humans; D009052:Leukemia Virus, Murine / Q000737:chemistry / Q000502:physiology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D011323:Primates / Q000821:virology; D011956:Receptors, Cell Surface / Q000378:metabolism; D014771:Virion / Q000737:chemistry* / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D015683:Gene Products, gag; D015693:Gene Products, nef; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; C103949:SERINC3 protein, human; C000602387:SERINC5 protein, human; D054311:nef Gene Products, Human Immunodeficiency Virus; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D020691:rab GTP-Binding Proteins