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Journal of Virology, July 2005, p. 8870-8877, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.8870-8877.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Specific Region of 37 Amino Acid Residues in the SPRY (B30.2) Domain of African Green Monkey TRIM5 Determines Species-Specific Restriction of Simian Immunodeficiency Virus SIVmac Infection

Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka,¹ BioResource Center, RIKEN Tsukuba Institute, Tsukuba,² Toyama Institute of Health, Toyama, Japan³

Received 2 December 2004/ Accepted 30 March 2005

Human immunodeficiency virus type 1 (HIV-1) efficiently enters cells of Old World monkeys but encounters a block before reverse transcription. This restriction is mediated by a dominant repressive factor. Recently, a member of the tripartite motif (TRIM) family proteins, TRIM5, was identified as a blocking factor in a rhesus macaque cDNA library. Among Old World monkey cell lines, the African green monkey kidney cell line CV1 is highly resistant to not only HIV-1 but also simian immunodeficiency virus SIVmac infection. We analyzed TRIM5 of CV1 cells and HSC-F cells, a T-cell line from a cynomolgus monkey, and found that both CV1- and HSC-F-TRIM5s could inhibit CD4-dependent HIV-1 infection, as well as vesicular stomatitis virus glycoprotein-mediated infection. CV1-TRIM5 could also inhibit SIVmac infection, whereas HSC-F-TRIM5 could not. In the SPRY (B30.2) domain of CV1-TRIM5, there was a 20-amino-acid duplication that was not present in HSC-F-TRIM5. A chimeric TRIM5 containing 37 amino acid residues from CV1-TRIM5, which spanned the 20-amino-acid duplication, in the background of HSC-F-TRIM5 fully gained the ability to inhibit SIVmac infection. Conversely, the mutant CV1-TRIM5 lacking the 20-amino-acid duplication completely lost the ability to restrict SIVmac infection. These findings clearly indicated that a specific region of 37 amino acid residues in the SPRY domain of CV1-TRIM5 contained a determinant of species-specific restriction of SIVmac.

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