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Journal of Virology, May 2000, p. 4404-4413, Vol. 74, No. 9
0022-538X/00/$04.00+0

N-Linked Glycosylation of CXCR4 Masks Coreceptor Function for CCR5-Dependent Human Immunodeficiency Virus Type 1 Isolates

Donald J. Chabot,1 Hong Chen,1 Dimiter S. Dimitrov,2 and Christopher C. Broder1,*

Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799,1 and Laboratory of Experimental and Computational Biology, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702-12012

Received 17 December 1999/Accepted 8 February 2000

The chemokine receptors CXCR4 and CCR5 are the principal coreceptors for infection of X4 and R5 human immunodeficiency virus type 1 (HIV-1) isolates, respectively. Here we report on the unexpected observation that the removal of the N-linked glycosylation sites in CXCR4 potentially allows the protein to serve as a universal coreceptor for both X4 and R5 laboratory-adapted and primary HIV-1 strains. We hypothesize that this alteration unmasks existing common extracellular structures reflecting a conserved three-dimensional similarity of important elements of CXCR4 and CCR5 that are involved in HIV envelope glycoprotein (Env) interaction. These results may have far-reaching implications for the differential recognition of cell type-dependent glycosylated CXCR4 by HIV-1 isolates and their evolution in vivo. They also suggest a possible explanation for the various observations of restricted virus entry in some cell types and further our understanding of the framework of elements that represent the Env-coreceptor contact sites.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814-4799. Phone: (301) 295-3401. Fax: (301) 295-1545. E-mail: cbroder{at}mxb.usuhs.mil.

Journal of Virology, May 2000, p. 4404-4413, Vol. 74, No. 9
0022-538X/00/$04.00+0


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