title: The Role of the Antiviral APOBEC3 Gene Family in Protecting Chimpanzees against Lentiviruses from Monkeys.
abstract: Cross-species transmissions of viruses from animals to humans are at the origin of major human pathogenic viruses. While the role of ecological and epidemiological factors in the emergence of new pathogens is well documented, the importance of host factors is often unknown. Chimpanzees are the closest relatives of humans and the animal reservoir at the origin of the human AIDS pandemic. However, despite being regularly exposed to monkey lentiviruses through hunting, chimpanzees are naturally infected by only a single simian immunodeficiency virus, SIVcpz. Here, we asked why chimpanzees appear to be protected against the successful emergence of other SIVs. In particular, we investigated the role of the chimpanzee APOBEC3 genes in providing a barrier to infection by most monkey lentiviruses. We found that most SIV Vifs, including Vif from SIVwrc infecting western-red colobus, the chimpanzee's main monkey prey in West Africa, could not antagonize chimpanzee APOBEC3G. Moreover, chimpanzee APOBEC3D, as well as APOBEC3F and APOBEC3H, provided additional protection against SIV Vif antagonism. Consequently, lentiviral replication in primary chimpanzee CD4(+) T cells was dependent on the presence of a lentiviral vif gene that could antagonize chimpanzee APOBEC3s. Finally, by identifying and functionally characterizing several APOBEC3 gene polymorphisms in both common chimpanzees and bonobos, we found that these ape populations encode APOBEC3 proteins that are uniformly resistant to antagonism by monkey lentiviruses.
authors.affiliation: Divisions of Human Biology and Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Lucie
authors.initials: L
authors.lastname: Etienne
authors.affiliation: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bibollet-Ruche
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Sudmant
authors.affiliation: Divisions of Human Biology and Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Lily I
authors.initials: LI
authors.lastname: Wu
authors.affiliation: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.affiliation: Divisions of Human Biology and Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Emerman
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003564:Cytidine Deaminase / Q000235:genetics* / Q000276:immunology; D016341:Genes, vif / Q000235:genetics; D000882:Haplorhini; D016086:Lentivirus / Q000235:genetics; D016180:Lentivirus Infections / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000276:immunology* / Q000821:virology*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D015302:Simian Immunodeficiency Virus / Q000235:genetics*
chemical_list: D003564:Cytidine Deaminase