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Risk factors influencing antibody responses to Kaposi's sarcoma-associated herpesvirus latent and lytic antigens in patients under antiretroviral therapy.

ABSTRACT: BACKGROUND:Kaposi's sarcoma-associated herpesvirus (KSHV) seropositivity and lytic antibody titer are predictors for Kaposi's sarcoma. METHODS:We examined demographic, viral, and immunologic factors that influence KSHV latent and lytic antibodies in HIV-infected patients. RESULTS:Detection rate of KSHV latent but not lytic antibodies was lower in patients with CD4 cells/mm3 less than 200 than greater than 200 (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.11-0.61) and CD8 cells/mm3 less than 400 than greater than 400 (OR, 0.26; 95% CI, 0.07-0.67). Overall seropositivity rate was higher in patients with CD4 cells/mm3 less than 200 than greater than 200 (OR, 2.34; 95% CI, 1.37-4.02) and HIV copies/mL greater than 400 than less than 400 (OR, 1.70; 95% CI, 1.09-2.65). Lytic antibody level was inversely correlated with CD4 count (P < 0.001). Lytic seropositivity (OR, 2.47; 95% CI, 1.35-4.50) and antibody level (adjusted difference mean optical density, 0.324; 95% CI, 0.16-0.46) were higher in patients with HIV infection greater than 15 than less than 15 years. Hispanics had higher lytic seropositivity rate (OR, 1.71; 95% CI, 1.07-2.73) and antibody level (adjusted difference mean optical density, 0.111; 95% CI, 0.03-0.18) than non-Hispanics. CONCLUSIONS:Lower CD4 and CD8 counts impair antibody response to KSHV latent antigens. Immune deterioration, long-term HIV infection, and Hispanic status are risk factors for Kaposi's sarcoma predictors.

SUBMITTER: Guadalupe M

PROVIDER: S-EPMC3051282 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Risk factors influencing antibody responses to Kaposi's sarcoma-associated herpesvirus latent and lytic antigens in patients under antiretroviral therapy.

Guadalupe Moraima M Pollock Brad H BH Westbrook Steven S Redding Spencer S Bullock Delia D Anstead Gregory G Agan Brian K BK Marconi Vincent C VC Barbieri Sharon S Sankar Vidya V Rebeles Jennifer J Flahive Yvette Y Schoolfield John J Wang Linding L Lei Xiufen X Dow Dorothy D Yeh Chih-Ko CK Dang Howard H Infante Anthony J AJ Gao Shou-Jiang SJ

Journal of acquired immune deficiency syndromes (1999) 20110101 1

<h4>Background</h4>Kaposi's sarcoma-associated herpesvirus (KSHV) seropositivity and lytic antibody titer are predictors for Kaposi's sarcoma.<h4>Methods</h4>We examined demographic, viral, and immunologic factors that influence KSHV latent and lytic antibodies in HIV-infected patients.<h4>Results</h4>Detection rate of KSHV latent but not lytic antibodies was lower in patients with CD4 cells/mm3 less than 200 than greater than 200 (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.11-0.61) ...[more]

PMID: 21084997

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Project description:UnlabelledKaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of commonly fatal malignancies of immunocompromised individuals, including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS). A hallmark of all herpesviruses is their biphasic life cycle-viral latency and the productive lytic cycle-and it is well established that reactivation of the KSHV lytic cycle is associated with KS pathogenesis. Therefore, a thorough appreciation of the mechanisms that govern reactivation is required to better understand disease progression. The viral protein replication and transcription activator (RTA) is the KSHV lytic switch protein due to its ability to drive the expression of various lytic genes, leading to reactivation of the entire lytic cycle. While the mechanisms for activating lytic gene expression have received much attention, how RTA impacts cellular function is less well understood. To address this, we developed a cell line with doxycycline-inducible RTA expression and applied stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative proteomics. Using this methodology, we have identified a novel cellular protein (AT-rich interacting domain containing 3B [ARID3B]) whose expression was enhanced by RTA and that relocalized to replication compartments upon lytic reactivation. We also show that small interfering RNA (siRNA) knockdown or overexpression of ARID3B led to an enhancement or inhibition of lytic reactivation, respectively. Furthermore, DNA affinity and chromatin immunoprecipitation assays demonstrated that ARID3B specifically interacts with A/T-rich elements in the KSHV origin of lytic replication (oriLyt), and this was dependent on lytic cycle reactivation. Therefore, we have identified a novel cellular protein whose expression is enhanced by KSHV RTA with the ability to inhibit KSHV reactivation.ImportanceKaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of fatal malignancies of immunocompromised individuals, including Kaposi's sarcoma (KS). Herpesviruses are able to establish a latent infection, in which they escape immune detection by restricting viral gene expression. Importantly, however, reactivation of productive viral replication (the lytic cycle) is necessary for the pathogenesis of KS. Therefore, it is important that we comprehensively understand the mechanisms that govern lytic reactivation, to better understand disease progression. In this study, we have identified a novel cellular protein (AT-rich interacting domain protein 3B [ARID3B]) that we show is able to temper lytic reactivation. We showed that the master lytic switch protein, RTA, enhanced ARID3B levels, which then interacted with viral DNA in a lytic cycle-dependent manner. Therefore, we have added a new factor to the list of cellular proteins that regulate the KSHV lytic cycle, which has implications for our understanding of KSHV biology.

Dataset Information

Risk factors influencing antibody responses to Kaposi's sarcoma-associated herpesvirus latent and lytic antigens in patients under antiretroviral therapy.

Publications

Risk factors influencing antibody responses to Kaposi's sarcoma-associated herpesvirus latent and lytic antigens in patients under antiretroviral therapy.

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