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Journal of Virology, May 2005, p. 6111-6121, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6111-6121.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The B30.2(SPRY) Domain of the Retroviral Restriction Factor TRIM5{alpha} Exhibits Lineage-Specific Length and Sequence Variation in Primates

Byeongwoon Song,1 Bert Gold,2 Colm O'hUigin,3 Hassan Javanbakht,1 Xing Li,1 Matthew Stremlau,1 Cheryl Winkler,3 Michael Dean,2 and Joseph Sodroski1,4*

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115,1 Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702-1201,2 SAIC-Frederick, Frederick, Maryland 21702-1201,3 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 021154

Received 23 September 2004/ Accepted 18 December 2004

Tripartite motif (TRIM) proteins are composed of RING, B-box 2, and coiled coil domains. Some TRIM proteins, such as TRIM5{alpha}, also possess a carboxy-terminal B30.2(SPRY) domain and localize to cytoplasmic bodies. TRIM5{alpha} 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 TRIM5{alpha} was analyzed by amplifying, cloning, and sequencing nonhuman primate TRIM5 orthologs. Lineage-specific expansion and sequential duplication occurred in the TRIM5{alpha} 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 TRIM5{alpha} 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 TRIM5{alpha} in innate immunity against retroviruses.

* Corresponding author. Mailing address: Dana-Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115. Phone: (617) 632-3371. Fax: (671) 632-4338. E-mail: joseph_sodroski{at}dfci.harvard.edu.

Journal of Virology, May 2005, p. 6111-6121, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6111-6121.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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