title: Retrovirus restriction by TRIM5alpha variants from Old World and New World primates.
abstract: The TRIM5alpha proteins of humans and some Old World monkeys have been shown to block infection of particular retroviruses following virus entry into the host cell. Infection of most New World monkey cells by the simian immunodeficiency virus of macaques (SIVmac) is restricted at a similar point. Here we examine the antiretroviral activity of TRIM5alpha orthologs from humans, apes, Old World monkeys, and New World monkeys. Chimpanzee and orangutan TRIM5alpha proteins functionally resembled human TRIM5alpha, potently restricting infection by N-tropic murine leukemia virus (N-MLV) and moderately restricting human immunodeficiency virus type 1 (HIV-1) infection. Notably, TRIM5alpha proteins from several New World monkey species restricted infection by SIVmac and the SIV of African green monkeys, SIVagm. Spider monkey TRIM5alpha, which has an expanded B30.2 domain v3 region due to a tandem triplication, potently blocked infection by a range of retroviruses, including SIVmac, SIVagm, HIV-1, and N-MLV. Tandem duplications in the TRIM5alpha B30.2 domain v1 region of African green monkeys are also associated with broader antiretroviral activity. Thus, variation in TRIM5alpha proteins among primate species accounts for the observed patterns of postentry restrictions in cells from these animals. The TRIM5alpha proteins of some monkey species exhibit dramatic lengthening of particular B30.2 variable regions and an expanded range of susceptible retroviruses.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA, USA.
authors.forename: Byeongwoon
authors.initials: B
authors.lastname: Song
authors.forename: Hassan
authors.initials: H
authors.lastname: Javanbakht
authors.forename: Michel
authors.initials: M
authors.lastname: Perron
authors.forename: Do Hyun
authors.initials: DH
authors.lastname: Park
authors.forename: Matthew
authors.initials: M
authors.lastname: Stremlau
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D044966:Anti-Retroviral Agents; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002427:Cebidae; D002478:Cells, Cultured; D002520:Cercopithecidae; D015497:HIV-1 / Q000254:growth & development; D009052:Leukemia Virus, Murine / Q000254:growth & development; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012190:Retroviridae / Q000254:growth & development*; D017422:Sequence Analysis, DNA; D015302:Simian Immunodeficiency Virus / Q000254:growth & development; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D044966:Anti-Retroviral Agents; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D011506:Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases