Expression and cytoplasmic: localisation of deoxyuridine triphosphate pyrophosphatase encoded by a human endogenous retrovirus

Many lentiviruses encode a dUTPase which may protect against toxic misincor poration of dUTP into cDNA during reverse transcription. However, the prima te lentiviruses HIV and SIV do not express a dUTPase. Significantly, the ho st genomes of these lentiviruses contain a multicopy endogenous retrovirus which is absent in non-primate genomes. In humans, this endogenous retrovir us is known as HERV-K and encodes a potential dUTPase sequence. Previously, we have suggested that HIV infection is complemented by a cytosolic dUTPas e derived from the dUTPase gene encoded by HERV-K. This study demonstrates expression of HERV-K dUTPase transcripts and protein in human cell lines us ing RT-PCR and western blot analysis. Immunocytochemistry showed that HERV- K dUTPase was predominantly located in cell cytoplasm when transiently expr essed in COS-1 cells. These data provide substantiation and support for the hypothesis above and is the first documentation of expression of an enzyme of nucleotide metabolism expressed by an endogenous retrovirus.