title: HIV-1 Group P is unable to antagonize human tetherin by Vpu, Env or Nef.
abstract: BACKGROUND
  A new subgroup of HIV-1, designated Group P, was recently detected in two unrelated patients of Cameroonian origin. HIV-1 Group P phylogenetically clusters with SIVgor suggesting that it is the result of a cross-species transmission from gorillas. Until today, HIV-1 Group P has only been detected in two patients, and its degree of adaptation to the human host is largely unknown. Previous data have shown that pandemic HIV-1 Group M, but not non-pandemic Group O or rare Group N viruses, efficiently antagonize the human orthologue of the restriction factor tetherin (BST-2, HM1.24, CD317) suggesting that primate lentiviruses may have to gain anti-tetherin activity for efficient spread in the human population. Thus far, three SIV/HIV gene products (vpu, nef and env) are known to have the potential to counteract primate tetherin proteins, often in a species-specific manner. Here, we examined how long Group P may have been circulating in humans and determined its capability to antagonize human tetherin as an indicator of adaptation to humans.
  
  
  RESULTS
  Our data suggest that HIV-1 Group P entered the human population between 1845 and 1989. Vpu, Env and Nef proteins from both Group P viruses failed to counteract human or gorilla tetherin to promote efficient release of HIV-1 virions, although both Group P Nef proteins moderately downmodulated gorilla tetherin from the cell surface. Notably, Vpu, Env and Nef alleles from the two HIV-1 P strains were all able to reduce CD4 cell surface expression.
  
  
  CONCLUSIONS
  Our analyses of the two reported HIV-1 Group P viruses suggest that zoonosis occurred in the last 170 years and further support that pandemic HIV-1 Group M strains are better adapted to humans than non-pandemic or rare Group O, N and P viruses. The inability to antagonize human tetherin may potentially explain the limited spread of HIV-1 Group P in the human population.
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89069, Ulm, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sauter
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hué
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Petit
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Plantier
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Towers
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Gupta
mesh_terms: D000220:Adaptation, Biological; D000483:Alleles; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003001:Cloning, Molecular; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006071:Gorilla gorilla; D057809:HEK293 Cells; D015658:HIV Infections / Q000378:metabolism / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010802:Phylogeny; D013045:Species Specificity; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514837:nef protein, Human immunodeficiency virus 1; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins