Previous Article | Next Article ![]()
J Virol, March 1998, p. 2509-2515, Vol. 72, No. 3
Laboratory of Molecular Microbiology,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, Maryland
20892-0460,1 and
Department of Pathology
and Laboratory Medicine, University of Pennsylvania, Philadelphia,
Pennsylvania 191042
Received 7 August 1997/Accepted 5 December 1997
The chemokine receptors CCR5 and CXCR4, in combination with CD4,
mediate cellular entry of macrophage-tropic (M-tropic) and T-cell-tropic strains of human immunodeficiency virus type 1 (HIV-1), respectively, while dualtropic viruses can use either receptor. We have
constructed a panel of chimeric viruses and envelope glycoproteins in
which various domains of the dualtropic HIV-1DH12 gp160
were introduced into the genetic background of an M-tropic HIV-1
isolate, HIV-1AD8. These constructs were employed in cell
fusion and virus infectivity assays using peripheral blood mononuclear
cells, MT4 T cells, primary monocyte-derived macrophages, or HOS-CD4
cell lines, expressing various chemokine receptors, to assess the
contributions of different gp120 subdomains in coreceptor usage and
cellular tropism. As expected, the dualtropic HIV-1DH12
gp120 utilized either CCR3, CCR5, or CXCR4, whereas
HIV-1AD8 gp120 was able to use only CCR3 or CCR5. We found
that either the V1/V2 or the V3 region of HIV-1DH12 gp120
individually conferred on HIV-1AD8 the ability to use
CXCR4, while the combination of both the V1/V2 and V3 regions increased
the efficiency of CXCR4 use. In addition, while the V4 or the V5 region
of HIV-1DH12 gp120 failed to confer the capacity to utilize
CXCR4 on HIV-1AD8, these regions were required in
conjunction with regions V1 to V3 of HIV-1DH12 gp120 for
efficient utilization of CXCR4. Comparison of virus infectivity analyses with various cell types and cell fusion assays revealed assay-dependent discrepancies and indicated that events occurring at
the cell surface during infection are complex and cannot always be
predicted by any one assay.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Identification of Determinants on a Dualtropic
Human Immunodeficiency Virus Type 1 Envelope Glycoprotein That Confer
Usage of CXCR4
*
Corresponding author. Mailing address: Laboratory of
Molecular Microbiology, NIH, NIAID, 9000 Rockville Pike, Bldg. 4, Rm. 339, Bethesda, MD 20892-0460. Phone: (301) 496-0576. Fax: (301) 402-0226. E-mail: MCho{at}nih.gov.
This article has been cited by other articles:
| J. Bacteriol. | Mol. Cell. Biol. | Microbiol. Mol. Biol. Rev. |
|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|