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Journal of Virology, July 2000, p. 6418-6424, Vol. 74, No. 14
Laboratory of
Immunoregulation1 and Laboratory of
Clinical Investigation,2 National Institute of
Allergy and Infectious Diseases, National Institutes of Health,
Bethesda, Maryland 20892
Received 28 December 1999/Accepted 14 April 2000
The capacity of human immunodeficiency virus (HIV) and simian
immunodeficiency virus (SIV) envelopes to transduce signals through
chemokine coreceptors on macrophages was examined by measuring the
ability of recombinant envelope proteins to mobilize intracellular calcium stores. Both HIV and SIV envelopes mobilized calcium via interactions with CCR5. The kinetics of these responses were similar to
those observed when macrophages were treated with MIP-1
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
CCR5 Signal Transduction in Macrophages by Human
Immunodeficiency Virus and Simian Immunodeficiency Virus
Envelopes

. Distinct differences in the capacity of envelopes to mediate calcium
mobilization were observed. Envelopes derived from viruses capable of
replicating in macrophages mobilized relatively high levels of calcium,
while envelopes derived from viruses incapable of replicating in
macrophages mobilized relatively low levels of calcium. The failure to
efficiently mobilize calcium was not restricted to envelopes derived
from CXCR4-utilizing isolates but also included envelopes derived from CCR5-utilizing isolates that fail to replicate in macrophages. We
characterized one CCR5-utilizing isolate, 92MW959, which entered macrophages but failed to replicate. A recombinant envelope derived from this virus mobilized low levels of calcium. When macrophages were
inoculated with 92MW959 in the presence of MIP-1
, viral replication
was observed, indicating that a CC chemokine-mediated signal provided
the necessary stimulus to allow the virus to complete its replication
cycle. Although the role that envelope-CCR5 signal transduction plays
in viral replication is not yet understood, it has been suggested that
envelope-mediated signals facilitate early postfusion events in viral
replication. The data presented here are consistent with this
hypothesis and suggest that the differential capacity of viral
envelopes to signal through CCR5 may influence their ability to
replicate in macrophages.
*
Corresponding author. Mailing address: NIH, Bldg. 10, Rm. 6A-08, 10 Center Dr., Bethesda, MD 20892. Phone: (301) 402-3547. Fax: (301) 480-5244. E-mail: jarthos{at}nih.gov.
Present address: Department of Clinical Medicine, University of
Cologne, Cologne, Germany.
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