PNAS study shows that TRIM5 and cyclophilin combine to protect against retroviruses.

An international team of researchers identified a two genes linked together in a monkey species, which protects against retroviruses. TRIM5 has been shown to protect certain species from retroviruses, but the human TRIM5 gene does not protect against HIV infection, notes Greg Towers, Ph.D., coordinator of the research and professor at University College London (UCL), infection and immunity.

The team found that Rhesus Macaques have a sophisticated antiviral arsenal that can protect them against retroviruses. By closely examining TRIM5 in this species, they demonstrated that in some monkeys another gene called cyclophilin is joined to the TRIM5 gene, generating a TRIMCyp fusion.

“Cyclophilin is very good at grabbing viruses as they enter cells. By fusing cyclophilin to TRIM5, a gene is made that is good at grabbing viruses and good at destroying them,” explains Sam Wilson, Ph.D., the paper’s first author and a postdoc in Dr. Towers’ lab.

“This is the second time that this fusion has been identified; a TRIMCyp gene also exists in South American Owl Monkeys and until now, this was thought to be an evolutionary one-off,” Dr. Wilson adds. 

The team now aims to develop humanized TRIMCyp that blocks HIV infection by artificially fusing human cyclophilin and human TRIM5.

The study was carried out by researchers at at UCL, the Biomedical Primate Research Centre, and Cambridge University. The findings will be published in Proceedings of the National Academy of Sciences.

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