Dichotomous effects of Plasmodium falciparum antigens on expression of human immunodeficiency virus (HIV) coreceptors and on infectability of CD4 cells by HIV.
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.
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
D000953:Antigens, Protozoan; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV