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Characterization of human herpes virus 8 genotypes in Kaposi's sarcoma patients in Tehran, Iran.

ABSTRACT: Kaposi's sarcoma (KS) associated with HHV8 is one of the common connective tissue malignancies especially in immunocompromised patients. The aim of the present study was to determine the common HHV8 genotypes in hospitalized patients in Tehran, Iran. A total of 36 archival paraffin-embedded KS tissue samples of patients with common characterization of KS were collected between 1999 to 2010 from hospitals in Tehran, Iran. After identifying the presence of HHV8 by amplification of its ORF 26 region, the ORF K1 region was amplified, sequenced and used for phylogenetic analysis. Among 30 ORF 26 positive cases, ORF K1 was amplified successfully in 14 cases. Consistent with other studies in Asia, subtype A (9 cases; 64.28%) and subtype C (5 cases; 35.71%) were detected by phylogenetic analysis. This result is in concordance with results from other countries of the region, however the ratio of genotype A to C is higher in our study compared to another study in the country.

SUBMITTER: Azadmanesh K

PROVIDER: S-EPMC3376924 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Characterization of human herpes virus 8 genotypes in Kaposi's sarcoma patients in Tehran, Iran.

Azadmanesh Kayhan K Norouzfar Zeinab Sadat ZS Sohrabi Amir A Safaie-Naraghi Zahra Z Moradi Afshin A Yaghmaei Parichehre P Naraghi Mona Masoumeh MM Arashkia Arash A Eslamifar Ali A

International journal of molecular epidemiology and genetics 20120515 2

Kaposi's sarcoma (KS) associated with HHV8 is one of the common connective tissue malignancies especially in immunocompromised patients. The aim of the present study was to determine the common HHV8 genotypes in hospitalized patients in Tehran, Iran. A total of 36 archival paraffin-embedded KS tissue samples of patients with common characterization of KS were collected between 1999 to 2010 from hospitals in Tehran, Iran. After identifying the presence of HHV8 by amplification of its ORF 26 regio ...[more]

PMID: 22724051

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Project description:Kaposi's sarcoma herpesvirus (KSHV) latent oncoprotein viral FLICE (FADD-like interferon converting enzyme)-like inhibitory protein (v-FLIP) or K13, a potent activator of NF-?B, has well-established roles in KSHV latency and oncogenesis. KSHV-induced COX-2 represents a novel strategy employed by KSHV to promote latency and inflammation/angiogenesis/invasion. Here, we demonstrate that v-FLIP/K13 promotes tumorigenic effects via the induction of host protein COX-2 and its inflammatory metabolite PGE2 in an NF-?B-dependent manner. In addition to our previous studies demonstrating COX-2/PGE2's role in transcriptional regulation of KSHV latency promoter and latent gene expression, the current study adds to the complexity that though LANA-1 (latency associated nuclear antigen) is utilizing COX-2/PGE2 as critical factors for its transcriptional regulation, it is the v-FLIP/K13 gene in the KSHV latency cluster that maintains continuous COX-2/PGE2 levels in the infected cells. We demonstrate that COX-2 inhibition, via its chemical inhibitors (NS-398 or celecoxib), reduced v-FLIP/K13-mediated NF-?B induction, and extracellular matrix (ECM) interaction-mediated signaling, mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) levels, and subsequently downregulated detachment-induced apoptosis (anoikis) resistance. vFLIP expression mediated the secretion of cytokines, and spindle cell differentiation activated the phosphorylation of p38, RSK, FAK, Src, Akt and Rac1-GTPase. The COX-2 inhibition in v-FLIP/K13-HMVECs reduced inflammation and invasion/metastasis-related genes, along with reduced anchorage-independent colony formation via modulating 'extrinsic' as well as 'intrinsic' cell death pathways. COX-2 blockade in v-FLIP/K13-HMVEC cells drastically augmented cell death induced by removal of essential growth/survival factors secreted in the microenvironment. Transformed cells obtained from anchorage-independent colonies of COX-2 inhibitor-treated v-FLIP/K13-HMVEC cells expressed lower levels of endothelial-mesenchymal transition genes such as slug, snail and twist, and higher expression of the tumor-suppressor gene, E-cadherin. Taken together, our study provides strong evidences that FDA-approved COX-2 inhibitors have great potential in blocking tumorigenic events linked to KSHV's oncogenic protein v-FLIP/K13.

Dataset Information

Characterization of human herpes virus 8 genotypes in Kaposi's sarcoma patients in Tehran, Iran.

Publications

Characterization of human herpes virus 8 genotypes in Kaposi's sarcoma patients in Tehran, Iran.

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