دورية
Molecular Basis for Cell Tropism of CXCR4-Dependent Human Immunodeficiency Virus Type 1 Isolates
| العنوان: | Molecular Basis for Cell Tropism of CXCR4-Dependent Human Immunodeficiency Virus Type 1 Isolates |
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| المؤلفون: | Tokunaga, Kenzo, Greenberg, Michael L., Morse, Michael A., Cumming, R. Ian, Lyerly, H. Kim, Cullen, Bryan R. |
| المصدر: | The Journal of Virology; August 2001, Vol. 75 Issue: 15 p6776-6785, 10p |
| مستخلص: | ABSTRACTLaboratory 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. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 0022538X 10985514 |
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| DOI: | 10.1128/JVI.75.15.6776-6785.2001 |