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Journal of Virology, May 2000, p. 4698-4704, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Retrovirus Vectors Bearing Jaagsiekte Sheep Retrovirus Env Transduce Human Cells by Using a New Receptor Localized to Chromosome 3p21.3

Sharath K. Rai,1 James C. DeMartini,2 and A. Dusty Miller1,3,*

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 981091; Department of Pathology, Colorado State University, Fort Collins, Colorado 805232; and Department of Pathology, University of Washington, Seattle, Washington 981953

Received 16 November 1999/Accepted 16 February 2000

Jaagsiekte sheep retrovirus (JSRV) is a type D retrovirus associated with a contagious lung tumor of sheep, ovine pulmonary carcinoma. Other than sheep, JSRV is known to infect goats, but there is no evidence of human infection. Until now it has not been possible to study the host range for JSRV because of the inability to grow this virus in culture. Here we show that the JSRV envelope protein (Env) can be used to pseudotype Moloney murine leukemia virus (MoMLV)-based retrovirus vectors and that such vectors can transduce human cells in culture. We constructed hybrid retrovirus packaging cells that express the JSRV Env and the MoMLV Gag-Pol proteins and can produce JSRV-pseudotype vectors at titers of up to 106 alkaline phosphatase-positive 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 inability of the JSRV-pseudotype vector to transduce hamster cells, we used the hamster cell line-based Stanford G3 panel of whole human genome radiation hybrids to phenotypically map the JSRV receptor (JVR) gene within the p21.3 region of human chromosome 3. JVR is likely a new retrovirus receptor, as none of the previously identified retrovirus receptors localizes to the same position. Several chemokine receptors that have been shown to serve as coreceptors for lentivirus infection are clustered in the same region of chromosome 3; however, careful examination shows that the JSRV receptor does not colocalize with any of these genes.

* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, Room C2-023, 1100 Fairview Ave. N., Seattle, WA 98109-1024. Phone: (206) 667-2890. Fax: (206) 667-6523. E-mail: dmiller{at}fhcrc.org.

Journal of Virology, May 2000, p. 4698-4704, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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