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Journal of Virology, January 1999, p. 205-213, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Microglia Express CCR5, CXCR4, and CCR3, but of These, CCR5 Is the Principal Coreceptor for Human Immunodeficiency Virus Type 1 Dementia Isolates

Andrew V. Albright,1 Joseph T. C. Shieh,1 Takayuki Itoh,2 Benhur Lee,3 David Pleasure,2 Michael J. O'Connor,4 Robert W. Doms,3 and Francisco González-Scarano1,*

Departments of Neurology and Microbiology1 and Department of Pathology and Laboratory Medicine,3 University of Pennsylvania School of Medicine, Division of Neurology, The Children's Hospital of Philadelphia,2 and Department of Neurosurgery, Thomas Jefferson University School of Medicine,4 Philadelphia, Pennsylvania

Received 22 July 1998/Accepted 9 October 1998

Microglia are the main human immunodeficiency virus (HIV) reservoir in the central nervous system and most likely play a major role in the development of HIV dementia (HIVD). To characterize human adult microglial chemokine receptors, we analyzed the expression and calcium signaling of CCR5, CCR3, and CXCR4 and their roles in HIV entry. Microglia expressed higher levels of CCR5 than of either CCR3 or CXCR4. Of these three chemokine receptors, only CCR5 and CXCR4 were able to transduce a signal in microglia in response to their respective ligands, MIP-1beta and SDF-1alpha , as recorded by single-cell calcium flux experiments. We also found that CCR5 is the predominant coreceptor used for infection of human adult microglia by the HIV type 1 dementia isolates HIV-1DS-br, HIV-1RC-br, and HIV-1YU-2, since the anti-CCR5 antibody 2D7 was able to dramatically inhibit microglial infection by both wild-type and single-round luciferase pseudotype reporter viruses. Anti-CCR3 (7B11) and anti-CXCR4 (12G5) antibodies had little or no effect on infection. Last, we found that virus pseudotyped with the DS-br and RC-br envelopes can infect cells transfected with CD4 in conjunction with the G-protein-coupled receptors APJ, CCR8, and GPR15, which have been previously implicated in HIV entry.

* Corresponding author. Mailing address: University of Pennsylvania, Department of Neurology, Clinical Research Building, 415 Curie Blvd., Room 264, Philadelphia, PA 19104-6146. Phone: (215) 662-3389. Fax: (215) 573-2029. E-mail: Scarano{at}mail.med.upenn.edu.

Journal of Virology, January 1999, p. 205-213, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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