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Journal of Virology, November 2007, p. 12210-12217, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.02499-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Novel TRIM5 Isoforms Expressed by Macaca nemestrina{triangledown}

Greg Brennan,1 Yury Kozyrev,2 Toshiaki Kodama,3 and Shiu-Lok Hu1,2,4*

Department of Microbiology, University of Washington, Seattle, Washington,1 Department of Pharmaceutics, University of Washington, Seattle, Washington,2 Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania,3 Washington National Primate Research Center, University of Washington, Seattle, Washington4

Received 13 November 2006/ Accepted 18 August 2007

The TRIM5 family of proteins contains a RING domain, one or two B boxes, and a coiled-coil domain. The TRIM5{alpha} isoform also encodes a C-terminal B30.2(SPRY) domain, differences within which define the breadth and potency of TRIM5{alpha}-mediated retroviral restriction. Because Macaca nemestrina animals are susceptible to some human immunodeficiency virus (HIV) isolates, we sought to determine if differences exist in the TRIM5 gene and transcripts of these animals. We identified a two-nucleotide deletion ({Delta}2) in the transcript at the 5' terminus of exon 7 in all M. nemestrina TRIM5 cDNA clones examined. This frameshift results in a truncated protein of 300 amino acids lacking the B30.2(SPRY) domain, which we have named TRIM5{theta}. This deletion is likely due to a single nucleotide polymorphism that alters the 3' splice site between intron 6 and exon 7. In some clones, a deletion of the entire 27-nucleotide exon 7 ({Delta}exon7) resulted in the restoration of the TRIM5 open reading frame and the generation of another novel isoform, TRIM5{eta}. There are 18 amino acid differences between M. nemestrina TRIM5{eta} and Macaca mulatta TRIM5{alpha}, some of which are at or near locations previously shown to affect the breadth and potency of TRIM5{alpha}-mediated restriction. Infectivity assays performed on permissive CrFK cells stably transduced with TRIM5{eta} or TRIM5{theta} show that these isoforms are incapable of restricting either HIV type 1 (HIV-1) or simian immunodeficiency virus infection. The expression of TRIM5 alleles incapable of restricting HIV-1 infection may contribute to the previously reported increased susceptibility of M. nemestrina to HIV-1 infection in vivo.

* Corresponding author. Mailing address: Washington National Primate Research Center, University of Washington, 3000 Western Ave., Seattle, WA 98121. Phone: (206) 616-9764. Fax: (206) 543-1589. E-mail: hus{at}bart.rprc.washington.edu

{triangledown} Published ahead of print on 5 September 2007.

Journal of Virology, November 2007, p. 12210-12217, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.02499-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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