Retrovirus vectors bearing jaagsiekte sheep retrovirus env transduce humancells by using a new receptor localized to chromosome 3p21.3

Jaagsiekte sheep retrovirus (JSRV) is a type D retrovirus associated with a contagious lung tumor of sheep, ovine pulmonary carcinoma. Other than shee p, JSRV is known to infect goats, but there is no evidence of human infecti on. Until now it has not been possible to study the host range for JSRV bec ause of the inability to grow this virus in culture. Here we show that the JSRV envelope protein (Enu) can be used to pseudotype Moloney murine leukem ia virus (MoMLV)-based retrovirus vectors and that such vectors can transdu ce human cells in culture. We constructed hybrid retrovirus packaging cells that express the JSRV Env and the MoMLV Gag-Pol proteins and ran produce J SRV-pseudotype vectors at titers of up to 10(6) alkaline phosphatase-positi ve focus-forming units/ml. Using this high-titer virus, we have studied the host range for JSRV, which includes sheep, human, monkey, bovine, dog, and rabbit cells but not mouse, rat, or hamster cells. Considering the inabili ty of the JSRV-pseudotype vector to transduce hamster cells, we used the ha mster cell line-based Stanford G3 panel of whole human genome radiation hyb rids to phenotypically map the JSRV receptor (JVR) gene within the p21.3 re gion of human chromosome 3. JVR is likely a new retrovirus receptor, as non e of the previously identified retrovirus receptors localizes to the same p osition. Several chemokine receptors that have been shown to serve as corec eptors for lentivirus infection are clustered in the same region of chromos ome 3; however, careful examination shows that the JSRV receptor does not c olocalize with any of these genes.