title: Dichotomous effects of Plasmodium falciparum antigens on expression of human immunodeficiency virus (HIV) coreceptors and on infectability of CD4 cells by HIV.
abstract: Many microbial coinfections accelerate the progression of human immunodeficiency virus (HIV) disease. Coinfections of Plasmodium falciparum malaria and HIV-1 are common; however, past studies of the effects of P. falciparum malaria on HIV-1 infection have shown little effect. The present study found that P. falciparum antigens (PF-Ags) variably regulate the expression of HIV-1 coreceptors and modulate the infectability of CD4 cells by HIV-1. Shortly after PF-Ag stimulation, CCR5 expression was down-regulated, but CXCR4 expression was modestly up-regulated. Subsequently, CCR5 expression on CD4 cells was induced. Infectability of PF-Ag-stimulated peripheral blood mononuclear cells (PBMC) by R5 HIV-1 was decreased, regardless of the duration of PF-Ag stimulation or CCR5 expression levels. In contrast, X4 HIV-1 replication was enhanced briefly in PBMC stimulated with PF-Ags but was inhibited with longer stimulation. Decreased HIV-1 infectability resulted, in part, from endogenous production of interferon-gamma. These results may explain why malaria previously did not appear to accelerate HIV-1 disease progression.
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology*; D019713:Receptors, CCR5 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015728:Receptors, HIV / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D014779:Virus Replication
chemical_list: D000953:Antigens, Protozoan; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV