Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infection

Abstract

Primate tripartite motif 5 alpha (TRIM5 alpha) proteins mediate innate intracellular resistance to retroviruses. In humans, TRIMS is located in a paralogous cluster that includes TRIM6, TRIM34, and TRIM22. Although TRIM6 and TRIM34 orthologs are found in other mammals, TRIM5 has to date been identified only in primates. Cow cells exhibit early blocks to infection by several retroviruses. We identify a cytoplasmic TRIM protein encoded by LOC505265 that is responsible for the restriction of infection by several lentiviruses and N-tropic murine leukemia virus in cow cells. Susceptibility of N-tropic murine leukemia virus to 505265-mediated restriction is determined primarily by residue 110 of the viral capsid protein. Phylogenetically, cow LOC505265 segregates with the TRIM5/TRIM6/TRIM34 group, but is not an ortholog of known TRIM genes. The B30.2/SPRY domain of 505265 exhibits long variable regions, a characteristic of the proteins encoded by this paralogous group, and shows evidence of positive selection. Apparently, cows have independently evolved a retroviral restriction factor from the same TRIM family that spawned TRIMS in primates. Particular features of this subset of cytoplasmic TRIM proteins may be conducive to the convergent evolution of virus-restricting factors.