title: Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infection.
abstract: Primate tripartite motif 5alpha (TRIM5alpha) proteins mediate innate intracellular resistance to retroviruses. In humans, TRIM5 is located in a paralogous cluster that includes TRIM6, TRIM34, and TRIM22. Although TRIM6 and TRIM34 orthologs are found in other mammals, TRIM5 has to date been identified only in primates. Cow cells exhibit early blocks to infection by several retroviruses. We identify a cytoplasmic TRIM protein encoded by LOC505265 that is responsible for the restriction of infection by several lentiviruses and N-tropic murine leukemia virus in cow cells. Susceptibility of N-tropic murine leukemia virus to 505265-mediated restriction is determined primarily by residue 110 of the viral capsid protein. Phylogenetically, cow LOC505265 segregates with the TRIM5/TRIM6/TRIM34 group, but is not an ortholog of known TRIM genes. The B30.2/SPRY domain of 505265 exhibits long variable regions, a characteristic of the proteins encoded by this paralogous group, and shows evidence of positive selection. Apparently, cows have independently evolved a retroviral restriction factor from the same TRIM family that spawned TRIM5 in primates. Particular features of this subset of cytoplasmic TRIM proteins may be conducive to the convergent evolution of virus-restricting factors.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Si
authors.forename: Nick
authors.initials: N
authors.lastname: Vandegraaff
authors.forename: Colm
authors.initials: C
authors.lastname: O'huigin
authors.forename: Byeongwoon
authors.initials: B
authors.lastname: Song
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.forename: Michel
authors.initials: M
authors.lastname: Perron
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Marasco
authors.forename: Alan
authors.initials: A
authors.lastname: Engelman
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D046368:Crows / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D003593:Cytoplasm / Q000378:metabolism* / Q000821:virology*; D019143:Evolution, Molecular; D015870:Gene Expression; D014644:Genetic Variation / Q000235:genetics; D015497:HIV-1 / Q000502:physiology; D009052:Leukemia Virus, Murine / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D048348:Reverse Transcription / Q000235:genetics
chemical_list: D008565:Membrane Proteins