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Molecular basis for cell tropism of CXCR4-dependent human immunodeficiency virus type 1 isolates.

Publication ,  Journal Article
Tokunaga, K; Greenberg, ML; Morse, MA; Cumming, RI; Lyerly, HK; Cullen, BR
Published in: J Virol
August 2001

Laboratory isolates of human immunodeficiency virus type 1 (HIV-1) that utilize CXCR4 as a coreceptor infect primary human macrophages inefficiently even though these express a low but detectable level of cell surface CXCR4. In contrast, infection of primary macrophages by primary CXCR4-tropic HIV-1 isolates is readily detectable. Here, we provide evidence suggesting that this difference in cell tropism results from a higher requirement for cell surface CXCR4 for infection by laboratory HIV-1 isolates. Transfected COS7 cells that express a high level of CD4 but a low level of CXCR4 were infected significantly more efficiently by two primary CXCR4-tropic HIV-1 isolates compared to the prototypic laboratory HIV-1 isolate IIIB. More importantly, overexpression of either wild-type or signaling-defective CXCR4 on primary macrophages dramatically enhanced the efficiency of infection by the laboratory HIV-1 isolate yet only modestly enhanced infection by either primary CXCR4-tropic virus. Overexpression of CD4 had, in contrast, only a limited effect on macrophage infection by the laboratory HIV-1, although infection by the primary isolates was markedly enhanced. We therefore conclude that the laboratory CXCR4-tropic HIV-1 isolate exhibits a significantly higher CXCR4 requirement for efficient infection than do the primary CXCR4-tropic isolates and that this difference can explain the poor ability of the laboratory HIV-1 isolate to replicate in primary macrophages. More generally, we propose that the cell tropisms displayed by different strains of HIV-1 in culture can largely be explained on the basis of differential requirements for cell surface CD4 and/or coreceptor expression levels.

Duke Scholars

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Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

August 2001

Volume

75

Issue

15

Start / End Page

6776 / 6785

Location

United States

Related Subject Headings

  • Virology
  • Tropism
  • Receptors, CXCR4
  • Mutagenesis
  • Macrophages
  • Humans
  • HIV-1
  • Gene Expression
  • Chlorocebus aethiops
  • Cells, Cultured
 

Citation

APA
Chicago
ICMJE
MLA
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Tokunaga, K., Greenberg, M. L., Morse, M. A., Cumming, R. I., Lyerly, H. K., & Cullen, B. R. (2001). Molecular basis for cell tropism of CXCR4-dependent human immunodeficiency virus type 1 isolates. J Virol, 75(15), 6776–6785. https://doi.org/10.1128/JVI.75.15.6776-6785.2001
Tokunaga, K., M. L. Greenberg, M. A. Morse, R. I. Cumming, H. K. Lyerly, and B. R. Cullen. “Molecular basis for cell tropism of CXCR4-dependent human immunodeficiency virus type 1 isolates.J Virol 75, no. 15 (August 2001): 6776–85. https://doi.org/10.1128/JVI.75.15.6776-6785.2001.
Tokunaga K, Greenberg ML, Morse MA, Cumming RI, Lyerly HK, Cullen BR. Molecular basis for cell tropism of CXCR4-dependent human immunodeficiency virus type 1 isolates. J Virol. 2001 Aug;75(15):6776–85.
Tokunaga, K., et al. “Molecular basis for cell tropism of CXCR4-dependent human immunodeficiency virus type 1 isolates.J Virol, vol. 75, no. 15, Aug. 2001, pp. 6776–85. Pubmed, doi:10.1128/JVI.75.15.6776-6785.2001.
Tokunaga K, Greenberg ML, Morse MA, Cumming RI, Lyerly HK, Cullen BR. Molecular basis for cell tropism of CXCR4-dependent human immunodeficiency virus type 1 isolates. J Virol. 2001 Aug;75(15):6776–6785.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

August 2001

Volume

75

Issue

15

Start / End Page

6776 / 6785

Location

United States

Related Subject Headings

  • Virology
  • Tropism
  • Receptors, CXCR4
  • Mutagenesis
  • Macrophages
  • Humans
  • HIV-1
  • Gene Expression
  • Chlorocebus aethiops
  • Cells, Cultured