title: Efficient SIVcpz replication in human lymphoid tissue requires viral matrix protein adaptation.
abstract: SIVs infecting wild-living apes in west central Africa have crossed the species barrier to humans on at least four different occasions, one of which spawned the AIDS pandemic. Although the chimpanzee precursor of pandemic HIV-1 strains must have been able to infect humans, the capacity of SIVcpz strains to replicate in human lymphoid tissues (HLTs) is not known. Here, we show that SIVcpz strains from two chimpanzee subspecies are capable of replicating in human tonsillary explant cultures, albeit only at low titers. However, SIVcpz replication in HLT was significantly improved after introduction of a previously identified human-specific adaptation at position 30 in the viral Gag matrix protein. An Arg or Lys at this position significantly increased SIVcpz replication in HLT, while the same mutation reduced viral replication in chimpanzee-derived CD4(+) T cells. Thus, naturally occurring SIVcpz strains are capable of infecting HLTs, the major site of HIV-1 replication in vivo. However, efficient replication requires the acquisition of a host-specific adaptation in the viral matrix protein. These results identify Gag matrix as a major determinant of SIVcpz replication fitness in humans and suggest a critical role in the emergence of HIV/AIDS.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6060, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bibollet-Ruche
authors.forename: Anke
authors.initials: A
authors.lastname: Heigele
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: Juliet L
authors.initials: JL
authors.lastname: Easlick
authors.forename: Julie M
authors.initials: JM
authors.lastname: Decker
authors.forename: Jun
authors.initials: J
authors.lastname: Takehisa
authors.forename: Gerald
authors.initials: G
authors.lastname: Learn
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sharp
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
mesh_terms: D000220:Adaptation, Biological; D019943:Amino Acid Substitution; D000818:Animals; D002478:Cells, Cultured; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D016180:Lentivirus Infections / Q000821:virology*; D016297:Mutagenesis, Site-Directed; D014066:Palatine Tonsil / Q000821:virology*; D002679:Pan troglodytes; D010802:Phylogeny; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D046509:Tissue Culture Techniques; D014763:Viral Matrix Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D015683:Gene Products, gag; D014763:Viral Matrix Proteins