Expression of CD4 controls the susceptibility of THP-1 cells to infection by R5 and X4 HIV type 1 isolates

ORCiD

Nejat Düzgüneş: 0000-0001-6159-1391

Department

Biomedical Sciences

Document Type

Article

Publication Title

AIDS Research and Human Retroviruses

ISSN

0889-2229

Volume

18

Issue

2

DOI

10.1089/08892220252779665

First Page

123

Last Page

131

Publication Date

3-2-2002

Abstract

The monocytic THP-1 cell line has been used to study HIV-monocyte/macrophage interactions and the relationship between differentiation, virus production, and virus latency. Undifferentiated THP-1 cells are susceptible to infection by T-tropic human immunodeficiency virus type 1 (HIV-1) isolates that use the coreceptor CXCR4 (X4 strains). Treatment with phorbol 12-myristate 13-acetate (PMA) induces differentiation of THP-1 cells into adherent macrophage-like cells, which are susceptible to M-tropic, CCR5-dependent isolates (R5 strains). The aim of this study was to determine whether variabilities observed in the susceptibility of THP-1 cells to HIV-1 infection may be related to the differential expression of CD4, CCR5, and CXCR4. Both propagation and PMA treatment of THP-1 cells resulted in a marked decrease in CD4-positive cells, whereas the expression of CCR5 and CXCR4 was not reduced during propagation. Both coreceptors were also relatively "resistant" to PMA-induced downregulation when compared with the low percentage of CD4-positive cells in differentiated cultures. In undifferentiated THP-1 cells, low CD4 expression significantly reduced the susceptibility of the cells to infection with the R5 HIV-1BaL isolate, whereas a PMA-induced decrease in CD4 expression reduced permissiveness of the cells to the X4 HIV-1IIIB isolate. Thus, cell surface CD4 plays a primary role in determining how efficiently THP-1 cells can be infected with the X4 and the R5 isolates.

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