title: Gene loss and adaptation to hominids underlie the ancient origin of HIV-1.
abstract: HIV-1 resulted from cross-species transmission of SIVcpz, a simian immunodeficiency virus that naturally infects chimpanzees. SIVcpz, in turn, is a recombinant between two SIV lineages from Old World monkeys. Lentiviral interspecies transmissions are partly driven by the evolution and capacity of viral accessory genes, such as vpx, vpr, and vif, to antagonize host antiviral factors, such as SAMHD1 and the APOBEC3 proteins. We show that vpx, which in other lentiviruses antagonizes SAMHD1, was deleted during the creation of SIVcpz. This genomic deletion resulted in the reconstruction of the overlapping vif gene by "overprinting," creating a unique vif that overlaps in its 3' end with the vpr gene and can antagonize hominid APOBEC3s. Moreover, passage of SIVs through chimpanzees facilitated the subsequent adaptation of HIV-1 to humans. Thus, HIV-1 originated through a series of gene loss and adaptation events that generated its chimpanzee precursor and lowered the species barrier to human infection.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Lucie
authors.initials: L
authors.lastname: Etienne
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sharp
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Matsen
authors.forename: Michael
authors.initials: M
authors.lastname: Emerman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D017353:Gene Deletion; D016346:Gene Products, vif / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016336:Gene Products, vpr / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D000882:Haplorhini; D015186:Hominidae / Q000821:virology*; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D010802:Phylogeny; D016415:Sequence Alignment; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D016346:Gene Products, vif; D016336:Gene Products, vpr