title: Down-modulation of primate lentiviral receptors by Nef proteins of simian immunodeficiency virus (SIV) of chimpanzees (SIVcpz) and related SIVs: implication for the evolutionary event at the emergence of SIVcpz.
abstract: It has been estimated that human immunodeficiency virus type 1 originated from the zoonotic transmission of simian immunodeficiency virus (SIV) of chimpanzees, SIVcpz, and that SIVcpz emerged by the recombination of two lineages of SIVs in Old World monkeys (SIVgsn/mon/mus in guenons and SIVrcm in red-capped mangabeys) and SIVcpz Nef is most closely related to SIVrcm Nef. These observations suggest that SIVrcm Nef had an advantage over SIVgsn/mon/mus during the evolution of SIVcpz in chimpanzees, although this advantage remains uncertain. Nef is a multifunctional protein which downregulates CD4 and coreceptor proteins from the surface of infected cells, presumably to limit superinfection. To assess the possibility that SIVrcm Nef was selected by its superior ability to downregulate viral entry receptors in chimpanzees, we compared its ability to down-modulate viral receptor proteins from humans, chimpanzees and red-capped mangabeys with Nef proteins from eight other different strains of SIVs. Surprisingly, the ability of SIVrcm Nef to downregulate CCR5, CCR2B and CXCR6 was comparable to or lower than SIVgsn/mon/mus Nef, indicating that ability to down-modulate chemokine receptors was not the selective pressure. However, SIVrcm Nef significantly downregulates chimpanzee CD4 over SIVgsn/mon/mus Nefs. Our findings suggest the possibility that the selection of SIVrcm Nef by ancestral SIVcpz is due to its superior capacity to down-modulate chimpanzees CD4 rather than coreceptor proteins.
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507, Japan.|Department of Medical Virology, Faculty of Life Sciences, Kumamoto University, Kumamoto 8608556, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kenta
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507, Japan.
authors.forename: Rokusuke
authors.initials: R
authors.lastname: Yoshikawa
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Yamada
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Misawa
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hirsch
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
authors.affiliation: CREST, Japan Science and Technology Agency, Saitama 3220012, Japan.|Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto 6068507, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sato
mesh_terms: D000818:Animals; D016664:Cercocebus; D019143:Evolution, Molecular; D015693:Gene Products, nef / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D017958:Lentiviruses, Primate / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D002679:Pan troglodytes; D010802:Phylogeny; D018419:Primate Diseases / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D011323:Primates; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D015693:Gene Products, nef; D011991:Receptors, Virus