title: The B30.2(SPRY) domain of the retroviral restriction factor TRIM5alpha exhibits lineage-specific length and sequence variation in primates.
abstract: Tripartite motif (TRIM) proteins are composed of RING, B-box 2, and coiled coil domains. Some TRIM proteins, such as TRIM5alpha, also possess a carboxy-terminal B30.2(SPRY) domain and localize to cytoplasmic bodies. TRIM5alpha has recently been shown to mediate innate intracellular resistance to retroviruses, an activity dependent on the integrity of the B30.2 domain, in particular primate species. An examination of the sequences of several TRIM proteins related to TRIM5 revealed the existence of four variable regions (v1, v2, v3, and v4) in the B30.2 domain. Species-specific variation in TRIM5alpha was analyzed by amplifying, cloning, and sequencing nonhuman primate TRIM5 orthologs. Lineage-specific expansion and sequential duplication occurred in the TRIM5alpha B30.2 v1 region in Old World primates and in v3 in New World monkeys. We observed substitution patterns indicative of selection bordering these particular B30.2 domain variable elements. These results suggest that occasional, complex changes were incorporated into the TRIM5alpha B30.2 domain at discrete time points during the evolution of primates. Some of these time points correspond to periods during which primates were exposed to retroviral infections, based on the appearance of particular endogenous retroviruses in primate genomes. The results are consistent with a role for TRIM5alpha in innate immunity against retroviruses.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA.
authors.forename: Byeongwoon
authors.initials: B
authors.lastname: Song
authors.forename: Bert
authors.initials: B
authors.lastname: Gold
authors.forename: Colm
authors.initials: C
authors.lastname: O'Huigin
authors.forename: Hassan
authors.initials: H
authors.lastname: Javanbakht
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Matthew
authors.initials: M
authors.lastname: Stremlau
authors.forename: Cheryl
authors.initials: C
authors.lastname: Winkler
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000235:genetics*; D002427:Cebidae / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation; D008969:Molecular Sequence Data; D010802:Phylogeny; D018419:Primate Diseases / Q000235:genetics / Q000821:virology; D011323:Primates / Q000235:genetics* / Q000821:virology; D017434:Protein Structure, Tertiary / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics* / Q000472:pathogenicity; D012192:Retroviridae Infections / Q000235:genetics / Q000662:veterinary* / Q000821:virology; D016415:Sequence Alignment; D013045:Species Specificity; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014774:Virulence
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases