HIV pathogenesis: 25 years of progress and persistent challenges

School of Medicine, University of California, San Francisco, California, USA.
AIDS (London, England) (Impact Factor: 5.55). 02/2009; 23(2):147-60. DOI: 10.1097/QAD.0b013e3283217f9f
Source: PubMed
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    • "HIV infection leads to reactivation and spread of herpesviruses, including HSV-1 and -2, in oral and genital mucosa [2], [3], [4], [5], [6], [7], [8], [9], [10]. HIV infection causes attenuation of the immune system by substantially depleting CD4+ T cells in peripheral blood, lymphoid organs, and mucosal tissues, leading to CD8+ T cell dysfunction [11], [12], [13]. HIV-mediated depletion and dysfunction of CD4+/CD8+ T immune cells can lead to the activation of herpesviruses [2], [3], [4], [5], [6], which are usually latent under normal immune surveillance [14]. "
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    ABSTRACT: Herpes simplex virus (HSV) types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD). Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.
    Full-text · Article · Feb 2014 · PLoS ONE
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    • "Human immunodeficiency virus (HIV) is a retrovirus that infects cells of the immune system, destroying or impairing their function, which leads to the occurrence of opportunistic infections and tumors [1]. Though the malfunction of the immune system and the decrease in the number and activity of CD4+ T cells signify the hallmark of HIV infection, it is notable that HIV can also impede with other cell lineages and tissues [2,3]. "
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    ABSTRACT: Hematological abnormalities are common in HIV positive patients. Of these, thrombocytopenia is a known complication which has been associated with progression of disease. However, its magnitude and associated factors in HAART naive HIV positive patients is not known in Ethiopia. Therefore, the aim of this study was to determine the prevalence and associated factors of thrombocytopenia in HAART naive HIV positive patients. A retrospective study was carried out among HAART naive HIV positive patients at Gondar University Hospital, Northwest Ethiopia, from September 2011 through August 2012. Socio-demographic variables and immunohematological (platelets and CD4+ T cells) values were carefully reviewed from medical records. Associated factors and outcomes were assessed using logistic regression. A total of 390 HAART naive HIV positive patients with a mean age of 33.65 years and a range of 18-70 years were reviewed. The overall prevalence of thrombocytopenia was 23(5.9 %). The mean CD4 count was 288 +/- 188.2 cells/muL. HIV patients whose age >= 50 years old were 2.5 times more likely to have thrombocytopenia and those patients whose CD4 count < 350 were 2.6 times more likely to have thrombocytopenia than HIV patients whose CD4 count >=500. However, CD4 count was not statistically associated with prevalence of thrombocytopenia (P > 0.05). As CD4 counts of HIV patients decreasing, they have more likely to have thrombocytopenia. Therefore, early diagnosis and treatment of thrombocytopenia in these patients are necessary.
    Full-text · Article · Jan 2014 · BMC Research Notes
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    • "Several strides have been made in understanding the molecular mechanisms of pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection since the discovery of the virus in 1983 [1] [2]. This understanding has highlighted several critical points in the HIV-1 lifecycle that can be targeted for development of anti-retroviral drugs [3]. "
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    ABSTRACT: Most antiretroviral drugs currently in use to treat an HIV-1 infection are chemically synthesized and lead to the development of viral resistance, as well as cause severe toxicities. However, a largely unexplored source for HIV-1 drug discovery is endophytic fungi that live in a symbiotic relationship with plants. These fungi produce biologically active secondary metabolites, which are natural products that are beneficial to the host. We prepared several hundred extracts from endophytic fungi of desert plants and evaluated the inhibitory effects on HIV-1 replication of those extracts that showed less than 30% cytotoxicity in T-lymphocytes. Those extracts that inhibited viral replication were fractionated in order to isolate the compounds responsible for activity. Multiple rounds of fractionation and antiviral evaluation lead to the identification of four compounds, which almost completely impede HIV-1 replication. These studies demonstrate that metabolites from endophytic fungi of desert plants can serve as a viable source for identifying potent inhibitors of HIV-1 replication.
    Full-text · Article · Jul 2013 · The Open Virology Journal
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