Kaposi's sarcoma (KS) is a common AIDS-Defining illness and epidemiological features suggest the involvement of a sexually transmitted agent in the etiology of AIDS-KS. Recently, DNA sequences of a new herpesvirus provisionally named KS-associated herpesvirus (KSHV)- Human herpesvirus-8 (HHV-8) were identified in AIDS-associated and in non-AIDS KS lesions. The hypothesis derived from this is that reactivation and lytic HHV-8 replication occur under the conditions of HIV-induced reduced immune-surveillance which may precede the development of clinical AIDS-KS. Ongoing studies have identified several genes encoding immunogenic HHV-8 proteins and glycoproteins. The focus now will be to test the hypothesis by further characterizing the HHV-8 proteins associated with latent and lytic infections and to examine critically the elicited serological responses. The following three major SPECIFIC AIMS have been formulated. To define and characterize the immunogenic HHV-8 antigens associated with latent and lytic replicative cycle. To compare and evaluate the serological responses against the selected immunogenic HHV-8 lytic and latent antigens. To determine the temporal correlation between serological responses and the development of AIDS-KS and to determine whether serological responses can serve as markers for the development and progression of AIDS-KS. These studies could be significant since if HHV-8 replication precedes the development of KS then this may have important implications in the assessment of therapeutic intervention of HHV-8 infection by anti-herpes viral drugs.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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AIDS and Related Research Study Section 3 (ARRC)
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Cremer, Kenneth J
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University of Kansas
Schools of Medicine
Kansas City
United States
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Veettil, Mohanan Valiya; Kumar, Binod; Ansari, Mairaj Ahmed et al. (2016) ESCRT-0 Component Hrs Promotes Macropinocytosis of Kaposi's Sarcoma-Associated Herpesvirus in Human Dermal Microvascular Endothelial Cells. J Virol 90:3860-3872
Gjyshi, Olsi; Roy, Arunava; Dutta, Sujoy et al. (2015) Activated Nrf2 Interacts with Kaposi's Sarcoma-Associated Herpesvirus Latency Protein LANA-1 and Host Protein KAP1 To Mediate Global Lytic Gene Repression. J Virol 89:7874-92
Gjyshi, Olsi; Flaherty, Stephanie; Veettil, Mohanan Valiya et al. (2015) Kaposi's sarcoma-associated herpesvirus induces Nrf2 activation in latently infected endothelial cells through SQSTM1 phosphorylation and interaction with polyubiquitinated Keap1. J Virol 89:2268-86
Bandyopadhyay, Chirosree; Veettil, Mohanan Valiya; Dutta, Sujoy et al. (2014) p130Cas scaffolds the signalosome to direct adaptor-effector cross talk during Kaposi's sarcoma-associated herpesvirus trafficking in human microvascular dermal endothelial cells. J Virol 88:13858-78
Valiya Veettil, Mohanan; Dutta, Dipanjan; Bottero, Virginie et al. (2014) Glutamate secretion and metabotropic glutamate receptor 1 expression during Kaposi's sarcoma-associated herpesvirus infection promotes cell proliferation. PLoS Pathog 10:e1004389
Singh, Vivek Vikram; Dutta, Dipanjan; Ansari, Mairaj Ahmed et al. (2014) Kaposi's sarcoma-associated herpesvirus induces the ATM and H2AX DNA damage response early during de novo infection of primary endothelial cells, which play roles in latency establishment. J Virol 88:2821-34
Gjyshi, Olsi; Bottero, Virginie; Veettil, Mohanan Valliya et al. (2014) Kaposi's sarcoma-associated herpesvirus induces Nrf2 during de novo infection of endothelial cells to create a microenvironment conducive to infection. PLoS Pathog 10:e1004460
Veettil, Mohanan Valiya; Bandyopadhyay, Chirosree; Dutta, Dipanjan et al. (2014) Interaction of KSHV with host cell surface receptors and cell entry. Viruses 6:4024-46
Bandyopadhyay, Chirosree; Valiya-Veettil, Mohanan; Dutta, Dipanjan et al. (2014) CIB1 synergizes with EphrinA2 to regulate Kaposi's sarcoma-associated herpesvirus macropinocytic entry in human microvascular dermal endothelial cells. PLoS Pathog 10:e1003941
Paul, Arun George; Chandran, Bala; Sharma-Walia, Neelam (2013) Concurrent targeting of eicosanoid receptor 1/eicosanoid receptor 4 receptors and COX-2 induces synergistic apoptosis in Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus associated non-Hodgkin lymphoma cell lines. Transl Res 161:447-68

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