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Journal of Virology, September 2003, p. 9723-9727, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9723-9727.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Early- and Intermediate-Stage Variants of Simian Immunodeficiency Virus Replicate Efficiently in Cells Lacking CCR5

Serene Forte,1,{dagger} Mary-Elizabeth Harmon,1 Mario J. Pineda,1,2 and Julie Overbaugh1*

Division of Human Biology, Fred Hutchinson Cancer Research Center,1 Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington2

Received 24 March 2003/ Accepted 6 June 2003

Primate lentiviruses are thought to use the chemokine receptor CCR5 as the major coreceptor for entry into cells. Here we show that some variants of simian immunodeficiency virus (SIV) replicate efficiently in peripheral blood mononuclear cells (PBMCs) lacking a functional CCR5. There were differences in the replication patterns of sequential variants that evolved during SIVMne infection; the late-stage pathogenic variants were unable to replicate in PBMCs lacking CCR5, whereas the early- and intermediate-stage viruses replicated as well in PBMCs lacking CCR5 as they did in cells with wild-type CCR5. The coreceptor specificities of these sequential variants were compared using indicator cell lines expressing known SIV coreceptors. Among the known SIV coreceptors, there were none that were functional for the early and intermediate variants but not the late-stage variants, suggesting that the coreceptor used for replication in PBMCs may be a coreceptor that has not yet been described. Because some variants replicate with high efficiency in peripheral blood cells using this as yet uncharacterized cellular receptor, this coreceptor may be important for viral entry of some target cell populations in the host.


* Corresponding author. Mailing address: Division of Human Biology, Fred Hutchinson Cancer Center, 1100 Fairview Ave. N., C3-168, Seattle, WA 98109-1024. Phone: (206) 667-3524. Fax: (206) 667-1535. E-mail: joverbau{at}fhcrc.org.

{dagger} Present address: Virology Department, Millipore Corporation, Bedford, MA 01730.


Journal of Virology, September 2003, p. 9723-9727, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9723-9727.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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