Disease relevance of Herpesvirus 8, Human

• At a position equivalent to the gene encoding the saimiri transforming protein (STP) of herpesvirus saimiri (HVS), Kaposi's sarcoma-associated herpesvirus (KSHV) contains a distinct open reading frame called K1 [1].
• We have used a novel conditional transgenic system to study the mechanisms of angioproliferation induced by viral G protein-coupled receptor (vGPCR), the constitutively active chemokine receptor encoded by human herpesvirus 8 (HHV8, also known as Kaposi sarcoma herpesvirus) [2].
• The list of these viral proteins includes BCL-2 homologues (BHRF1 of EBV; KSBCL-2 of KSHV), an inhibitor of apoptosis (IAP) resembling Survivin (KSHV K7), proteins that alter mitochondrial ion permeability and/or membrane potential (HBV HBx, HPV E[wedge]14, HCV p7, and HTLV-1 p13(II)), and K15 of KSHV, a protein with undefined function [3].
• We demonstrate that PEL cell lines containing HHV-8 without and with coinfection with Epstein-Barr virus responded to the antiseizure medication valproate with entry into the lytic cascade and production of infectious virus [4].
• This report describes a patient with human immunodeficiency virus who was followed up clinically and by quantitative polymerase chain reaction for KSHV DNA sequences in PBMCs for more than 3 years following the diagnosis of KSHV-related MCD [5].

High impact information on Herpesvirus 8, Human

• HHV-8 envelope glycoprotein B possesses the RGD motif known to interact with integrin molecules, and HHV-8 infectivity was inhibited by RGD peptides, antibodies against RGD-dependent alpha3 and beta1 integrins, and by soluble alpha3beta1 integrin [6].
• These findings implicate a role for alpha3beta1 integrin and the associated signaling pathways in HHV-8 entry into the target cells [6].
• Further, HHV-8 infection induced the integrin-mediated activation of focal adhesion kinase (FAK) [6].
• Identification of the highly variable K1 gene sequence of the HHV-8 genome in both the donor's peripheral-blood cells and the recipients' serum confirmed that transmission had occurred [7].
• A novel viral mechanism for dysregulation of beta-catenin in Kaposi's sarcoma-associated herpesvirus latency [8].

Chemical compound and disease context of Herpesvirus 8, Human

• We show here that the phenotypic changes induced by the kaposin A protein of human herpesvirus 8 are mediated through its direct interaction with cytohesin-1, a guanine nucleotide exchange factor for ARF GTPases and regulator of integrin-mediated cell adhesion [9].
• Five patients demonstrated KSHV/HHV-8 DNA in their PBMCs during administration of intravenous foscarnet and/or ganciclovir [10].
• Cidofovir on HHV-8 in BCBL-1 cells [11].
• Identification of an immunoreceptor tyrosine-based activation motif of K1 transforming protein of Kaposi's sarcoma-associated herpesvirus [12].
• Remission of HHV-8 and HIV-associated multicentric Castleman disease with ganciclovir treatment [13].

Biological context of Herpesvirus 8, Human

• G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator [14].
• p53 inhibition by the LANA protein of KSHV protects against cell death [15].
• The lytic switch protein of KSHV activates gene expression via functional interaction with RBP-Jkappa (CSL), the target of the Notch signaling pathway [16].
• The B cell-tropic murine gammaherpesvirus-68 (MHV-68) is related to the Kaposi's sarcoma-associated herpesvirus (KSHV), but whereas KSHV expresses small chemokine homologues, MHV-68 encodes a broad spectrum chemokine binding protein (M3) [17].
• Deregulated signal transduction by the K1 gene product of Kaposi's sarcoma-associated herpesvirus [18].

Anatomical context of Herpesvirus 8, Human

• We show that the HHV-8-encoded IL-6 homologue (vIL-6) shares functional properties with endogenous IL-6 proteins and that both vIL-6 and vMIP-1 transcripts are present at high levels following butyrate induction of an HHV-8' BCBL cell line [19].
• We have examined the susceptibility of C.B-17 scid/scid mice implanted with human fetal thymus and liver grafts (SCID-hu Thy/Liv mice) to KSHV infection [20].
• The human herpesvirus 8 chemokine receptor vGPCR triggers autonomous proliferation of endothelial cells [2].
• FINDINGS: HHV-8 ORF 26 DNA was detected in significantly higher proportions of sarcoid than of non-sarcoid tissue samples from lung (8/8 vs 0/54; p < 0.0001), lymph nodes (26/27 vs 6/29; p < 0.0001), skin (2/2 vs 0/17; p = 0.006), and oral tissues (2/2 vs 1/13; p = 0.029) [21].
• In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium [22].

Gene context of Herpesvirus 8, Human

• Therefore, manipulation of the stability and function of IRF7 by the KSHV RTA transcription factor provides an unexpected regulatory strategy for circumventing the innate immune defence system [23].
• Cyclin D family members are cellular protooncogenes, and their viral homologues in the Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus type 8 [HHV-8]) and the closely related Herpesvirus saimiri have been implicated as putative cofactors of viral transformation and pathogenesis [24].
• Our results demonstrate for the first time, to our knowledge, that KSHV vFLIP K13 is required for the growth and proliferation of PEL cells and alternative NF-kappa B pathway plays a key role in this process [25].
• These findings suggest that KSHV may promote oncogenesis in PEL by expressing v-cyclin, which both overrides negative cell cycle controls present in the PEL precursor cells and induces a strong proliferative signal via CDK6 kinase activity [26].
• Transcriptional activation of nuclear factor-kappaB, as induced by the KS-promoting factor TNF-alpha, the HIV-1 Tat protein, or the human herpesvirus 8 protein ORF74, was inhibited by ritonavir [27].

Analytical, diagnostic and therapeutic context of Herpesvirus 8, Human

• The results of this HHV-8 antibody survey suggest that this rapid ELISA assay can be used to screen large numbers of sera to find those at risk for developing KS [28].
• Additionally, all sera from MM patients were negative for HHV-8 IgG by immunofluorescence [29].
• Antibodies to KSHV are detectable in the sera from most transplant recipients before initiation of immunosuppressive treatment suggesting that KS among immunosuppressed transplant patients is primarily due to virus reactivation [30].
• High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric castleman disease in HIV-infected patients [31].
• A human herpesvirus-8 (HHV-8) enzyme-linked immunosorbent assay (ELISA) with a whole virus lysate as antigen was developed and used to measure the seroprevalence rate and levels of IgG antibodies to HHV-8 in sera/plasma of various patient groups and blood donors [28].

References