Abstract
BACKGROUND: TRIM5α and TRIMCyp are cytoplasmic proteins that bind incoming retroviral capsids and mediate early blocks to viral infection. TRIM5 proteins form cytoplasmic bodies, which are highly dynamic structures. So far, TRIM5 proteins have been found only in the cytoplasm of cells. Interestingly, other proteins from the TRIM family localize to the nucleus. Therefore, we tested the possibility that TRIM5 proteins traffic to the nucleus and the impact of this trafficking on retroviral restriction. RESULTS: Here we report that the TRIM5α proteins of two Old World primates, humans and rhesus monkeys, are transported into the nucleus and are shuttled back to the cytoplasm by a leptomycin B-sensitive mechanism. In leptomycin B-treated cells, these TRIM5α proteins formed nuclear bodies that also contained TRIM19 (PML). Deletion of the amino terminus, including the linker 1 (L1) region, resulted in TRIM5α proteins that accumulated in nuclear bodies. Leptomycin B treatment of TRIM5α-expressing target cells only minimally affected the restriction of retrovirus infection. CONCLUSIONS: We discovered the ability of human and rhesus TRIM5α to shuttle into and out of the nucleus. This novel trafficking ability of TRIM5α proteins could be important for an as-yet-unknown function of TRIM5α.