title: The Potency of Nef-Mediated SERINC5 Antagonism Correlates with the Prevalence of Primate Lentiviruses in the Wild.
abstract: The cellular factor serine incorporator 5 (SERINC5) impairs HIV-1 infectivity but is antagonized by the viral Nef protein. We analyzed the anti-SERINC5 activity of Nef proteins across primate lentiviruses and examined whether SERINC5 represents a barrier to cross-species transmissions and/or within-species viral spread. HIV-1, HIV-2, and SIV Nefs counteract human, ape, monkey, and murine SERINC5 orthologs with similar potency. However, HIV-1 Nefs are more active against SERINC5 than HIV-2 Nefs, and chimpanzee SIV (SIVcpz) Nefs are more potent than those of their monkey precursors. Additionally, Nefs of HIV and most SIVs rely on the dileucine motif in the C-terminal loop for anti-SERINC5 activity, while the Nef from colobus SIV (SIVcol) evolved different inhibitory mechanisms. We also found a significant correlation between anti-SERINC5 potency and the SIV prevalence in the respective ape and monkey species. Thus, Nef-mediated SERINC5 antagonism may determine the ability of primate lentiviruses to spread within natural hosts.
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Heigele
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Dorota
authors.initials: D
authors.lastname: Kmiec
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Regensburger
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Langer
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Peiffer
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Stürzel
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sauter
authors.affiliation: UMI233, TransVIHMI, Institut de Recherche pour le Développement and Université Montpellier, Montpellier 34394, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Virus-Cell Interaction Group, CIBIO, University of Trento, 38123 Povo - Trento, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pizzato
authors.affiliation: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Learn
authors.affiliation: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bhahn@upenn.edu.
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany. Electronic address: frank.kirchhoff@uni-ulm.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D015498:HIV-2 / Q000276:immunology / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D011323:Primates; D016097:Simian Acquired Immunodeficiency Syndrome / Q000453:epidemiology* / Q000635:transmission / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: C429284:NEF protein, SIV; D054334:Viral Regulatory and Accessory Proteins; D037521:Virulence Factors; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C514838:nef protein, Human immunodeficiency virus 2