title: Expression of CD4 controls the susceptibility of THP-1 cells to infection by R5 and X4 HIV type 1 isolates.
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-1(BaL) isolate, whereas a PMA-induced decrease in CD4 expression reduced permissiveness of the cells to the X4 HIV-1(IIIB) 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.
authors.affiliation: Department of Microbiology, University of the Pacific School of Dentistry, San Francisco, California 94115, USA. kkonopka@sf.uop.edu
authors.forename: Krystyna
authors.initials: K
authors.lastname: Konopka
authors.forename: Nejat
authors.initials: N
authors.lastname: Düzgüneş
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D015536:Down-Regulation; D015726:Giant Cells; D015497:HIV-1 / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D015704:CD4 Antigens; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D013755:Tetradecanoylphorbol Acetate