ABSTRACT
OBJECTIVE: To investigate the in vitro effects of ellagic acid on HIV-1 replication. METHODS: Anti-HIV-1 activity of ellagic acid was determined in vitro using X4-tropic HIV-1NPO3 and R5-tropic pBaL Env-recombinant virus. Anti-HIV-1NPO3 activity of ellagic acid was investigated at a multiplicity of infection (MOI) of 0.01. Anti-HIV-1 integrase and protease activities of ellagic acid were tested using in vitro integration and proteolytic cleavage assays. RESULTS: Ellagic acid, added either before or after HIV-1NPO3 exposure, suppressed replication of the virus in C8166 cells up to 34%. Ellagic acid showed an anti-integrase IC50 of 8.7 µM. No cytotoxicity of ellagic acid at concentrations ranging from 12.5 to 100 µM was observed. CONCLUSION: We conclude that ellagic acid can inhibit HIV-1 infection without cytotoxicity. Thus, it may be a new effective agent that has potential to be developed as a novel microbicide against HIV-1.
Subject(s)
Ellagic Acid/pharmacology , HIV Infections/prevention & control , HIV-1/drug effects , Virus Replication/drug effects , CD4-Positive T-Lymphocytes/physiology , Cell Line , Cell Survival/drug effects , HIV Integrase/drug effects , HIV Protease/drug effects , HIV-1/enzymology , HumansABSTRACT
HIV-associated dementia (HAD) is not firmly established in patients with circulating recombinant form (CRF) 01_AE HIV-1. In this study, we compared neuropsychological performance among 15 Thai individuals with HAD, 15 Thai individuals without HAD, and 30 HIV-negative control subjects. HIV-1 participants were highly active anti-retroviral therapy naive and matched by age, education, and CD4 count. Neuropsychological testing abnormalities were identified in most cognitive domains among HAD vs HIV-negative participants, confirming the presence of HAD in CRF01_AE.
Subject(s)
AIDS Dementia Complex/virology , HIV-1/classification , HIV-1/genetics , Mental Disorders/virology , Nervous System Diseases/virology , Recombination, Genetic , AIDS Dementia Complex/blood , AIDS Dementia Complex/psychology , Adult , Cognition , Cohort Studies , Female , Humans , Male , Neuropsychological Tests , Severity of Illness IndexABSTRACT
The objective of this study was to determine changes in Th1/Th2 cytokine production at the cellular level which occur during the progression of HIV-1 subtype E infection in Thai children born to HIV-1 subtype E infected mothers. Mitogen stimulated whole blood cultures from 12 uninfected and 27 HIV-1 subtype E infected Thai children were stained intracellularly with fluorescein labelled monoclonal antibodies against Interleukin (IL)-2 and IFN-gamma (Th1 cytokines) and IL-4 (Th2 cytokine). Additionally, co-staining of CD4+ and CD8+ T cells was performed. Results were analyzed by two and three color flow cytometry. The percentage of IFN-gamma expressing cells in CD4+ T cells was increased in HIV-1 subtype E infected Thai children with mild and moderate immunosuppression (Immunological categories 1 + 2, Centers for Diseases Control and Prevention (CDC) staging system, 1994). The percentages of IFN-gamma expression was continuously enhanced accompanied by remaining preserved in the proportion of IL-2 producing T cells in HIV-1 subtype E infected Thai children with severe immunosuppression (Immunological category 3, CDC staging system, 1994). The percentages of IFN-gamma expression was continuously augmented whereas the proportion of IL-2 producing T cells remained unchanged in HIV-1 subtype E infected Thai Children with severe immunosuppression (immunological category 3, CDC staging system, 1994). The percentage of Th2 cytokine producing cells within the CD4+ ad CD8+ T cells increased in HIV-1 subtype E infected individuals and showed a significant difference in HIV-1 subtype E infected Thai children with AIDS compared with uninfected infants. These results suggest that in vertically acquired HIV-1 infection with severe immunosuppression, the percentages of IL-2 producing CD4+ T cell was consistent but the percentages of IL-4 and IFN-gamma producing cell were increased. Similar results were found for CD8+ T cells in which IL-4 producing cells were increased in conjunction with a remaining in the number of IL-2 producing cells in HIV-1 subtype E infected Thai children. Thus, changes in the Th1 and Th2 cytokine pattern during HIV-1 infection may contribute to the prognosis of HIV disease in children.