The function and diversity of the antiretroviral restriction factors TRIM5alpha and TRIMCyp in Old World primates

Abstract

The retroviral restriction factors TRIM5α and TRIMCyp, encoded in the <italic>TRIM5</italic> gene, prevent cross-species transmission of retroviruses in primates. In macaques (genus <italic>Macaca</italic>), TRIMCyp evolved through the retrotransposition of a cyclophilin A sequence into the <italic>TRIM5</italic> gene. In this work, I examine the evolutionary origin and geographic distribution of TRIMCyp, and I describe functional variability in both TRIM5α and TRIMCyp. I focus on <italic>M. sylvanus</italic>, because of its status as an evolutionary outgroup, and on <italic>M. fascicularis</italic>, which is commonly used as a model species for AIDS research. I show that TRIMCyp evolved approximately 5-6 million years ago in the common ancestor of the Asian macaques, after their divergence from <italic>M. sylvanus</italic>, and that the genetic changes leading to TRIMCyp expression are variably distributed in <italic>M. fascicularis</italic> populations. I demonstrate that multiple TRIM5α and TRIMCyp alleles, with different antiviral specificities, are present in the <italic>M. sylvanus</italic> and <italic>M. fascicularis</italic> populations, respectively. Finally, I show that coexpression of <italic>M. fascicularis</italic> TRIM5α and TRIMCyp does not lead to the loss of restriction capability by either protein. The functional diversity of TRIM5α and TRIMCyp restriction factors in macaques may have important consequences for their use as HIV/AIDS models. This work helps to define some of the parameters that may affect retroviral infection of nonhuman primate species.