Kaposi sarcoma-associated herpesvirus (KSHV): molecular biology and oncogenesis. – PubMed

In this study, we show that EZH2 elevation is associated with epigenetic modifications of Kaposi sarcoma-associated herpesvirus (KSHV), an oncogenic virus that promotes the development of Kaposi sarcoma and other malignancies that occur in patients with chronic HIV infections. Unlike acute-transforming animal viruses, however, human tumor-associated viruses lead to malignancies with a prolonged latency and in conjunction with other environmental and host-related cooperating events. Here, we review the current clinical insights into KSHV-associated cancers and discuss scientific insights into the pathobiology of KS, primary effusion lymphoma, and multicentric Castleman’s disease. Latent Epstein-Barr virus (EBV) infection is associated with several malignancies, including Burkitt’s lymphoma, Hodgkin’s disease, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disease (LPD). We included 189 159 subjects (26 972 with KS). Address correspondence to: Blossom Damania, 450 West Drive, CB# 7295, Rm 32-026, Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

The siRNA-mediated knockdown of vIRF3 in KSHV-positive PEL cells led to a significant decrease in endogenous c-Myc protein levels (116). Our consortium will be led by three principal investigators with highly complementary expertise (Satish Gopal MD, clinical research;Sam Phiri PhD, implementation science;Blossom Damania PhD, virology). Further studies are required to elucidate the exact mechanism used by KSHV to promote bladder cancer progression. In vivo studies showed that in the absence of all T cells, NK cells delayed tumor development, but they could not prevent it, suggesting that the PyV-induced tumors developed an immune-escape mechanism.35 Possible ways for the tumors to escape the control of NK cells would be to prevent NK cell migration to the tumors, to make NK cells dysfunctional, or to block the recognition of the tumors. 99-5-02). Human retroviruses cause malignancy via direct effects as well as through interactions with other oncogenic herpesviruses and other viruses.

Studies on specific cancer-associated viruses, e.g. Other oncoviruses include Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). Relative differences in the ability to mount cytotoxic T-cell responses have been noted among mouse strains for several years, and recent evidence suggests that immunogenetic determinants in humans may play similar roles. Antiviral treatments against chronic HBV and HCV infections have achieved this goal, with significant reduction in the incidence of hepatocellular carcinoma in treated patients. Detection of the virus is a strong argument in favour of a diagnosis of Hodgkin lymphoma, in particular in cases where differential diagnosis with a Hodgkin‐like anaplastic large cell lymphoma is difficult (see also section on controversies). Virally induced cell responses are color coded according to the Hallmarks of Cancer to which they correspond (on the right).

Indeed, EBV was discovered because of its presence in African Burkitt’s lymphoma and has been shown in the ensuing 35 years or so to be associated with a growing list of neoplasms—particularly, but not exclusively, tumors of lymphoid or epithelial origin (2). We propose that the retention of viral proteins induces inflammation, endoplasmic reticulum stress, and genomic instability in HL, NPC, and hepatocellular carcinoma, whereby the viral oncoproteins may play additional transactivational roles to induce host genes for transformation, invasion, and metastasis. The 5′-AMP-activated protein kinase (AMPK) is a cellular energy sensor regulating metabolic homeostasis. Popovic and Garzino-Demo are collaborating with Dr. Learn more about Kaposi sarcoma. The relevance of viral infection to human cancer development has often been debated.

Durst, M., Gissmann, L., Ikenberg, H. Moreover, a common theme for DNA tumor viruses emerged since it has been demonstrated that oncoproteins encoded by SV40, adenovirus, and HPV share similar capacities for inactivating both the Rb and p53 tumor suppressors [ 45 ]. Liver cancer or hepatocellular carcinoma (HCC) globally is one of the commonest malignancies, particularly in China. Mutations of these residues did not alter LANA’s DNA binding capabilities but diminished the interaction with cellular chromatin bromodomain (BRD) proteins, which play a role in latent replication and maintenance 16, 17, 19. Despite many resemblances, these EBV-linked lymphoproliferative disorders display heterogeneity at the clinical and the molecular level. Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF) Prevent All Cigarette Trafficking Act of 2009 (PACT Act) is a an act signed by President Barack Obama on March 31, 2010 designed to prevent tobacco smuggling and to enforce tobacco sales and tax laws.

We prospectively characterized KSHV viral load (VL), viral (v) and hIL-6, and other cytokines during KSHV-MCD flare and remission in 21 patients with 34 flares and 20 remissions. Amer. Serum hIL-6 level, IL-10 level, KSHV viral load, and other parameters were measured to further evaluate the immunologic and virologic milieu in case patients and control patients. ANGPT2, angiopoietin 2; CCL5, chemokine, CC motif, ligand 5; CCR5, chemokine, CC motif receptor 5; CXCL12, chemokine CXC motif, ligand 12; EdnA, Endothelin A; NRP, neuropilin; PDGF, platelet-derived growth factor; TGFβ, transforming growth factor-β; TNF, tumour necrosis factor; VEGF, vascular endothelial growth factor. None of the studies were designed as epidemiologic studies to determine if the presence of the virus was significantly associated with breast cancer. Kaposi’s sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 (HHV8)) is the infectious cause of this neoplasm.

Therefore, Nm23-H1 regulation of pathogenesis may be tumor specific, and identification of regulatory mechanisms for Nm23-H1 expression and cellular localization would facilitate a better understanding of type-specific, Nm23-H1-associated cancer progression. This finding supports the notion that constitutively activated STAT6 in PEL cell lines is associated with KSHV-mediated reduced SHP1 expression at the protein, rather than transcriptional, level. Hybridized signals not detected in non-neoplastic gastric epithelium. (C) After the 24-h scratch assay time point, cell lysates were harvested and subjected to SDS-PAGE and Western blotting for the proteins indicated to confirm CEACAM1 siRNA knockdown. Identified ORFs and encoded proteins are indicated in the figure. The paleoanthropologist Louis Leakey discovered the first known case of homonid cancer in an archaeological jawbone, which was suggestive of Burkitt’s lymphoma occurring at least 300,000 years ago (see timeline).

In adults, VEGFR-3 is predominantly expressed by lymphatic endothelium and tumor vasculature and by a subset of normal endothelial cells, including HMVECs56 (). The UCH human subclass consists of … Viral replication inhibitors (e.g. Moreover, mice haploinsufficient for TSC2 are predisposed to vascular sarcomas remarkably similar to KS. In addition, the treatment of EBVaGC is also briefly discussed. Infection with the bacterium Helicobacter pylori is responsible for nearly 90% of stomach cancers worldwide and approximately 33% of all infection-related cancers.

Analysis of mRNA levels for K3, ORF49, and ORF64 during KSHV primary infection at 1, 2, 4, and 7 days p.i. (B) Activity of the full-length Ang-2 promoter reporter pEBS1 cotransfected with the DNs at 52 hpi. The tumor suppressor pRb sequesters E2F, a transcription factor required for G1/S transition (41). By continuing to browse this site you agree to us using cookies as described in About Cookies. Double-stranded DNA genome of EBV viruses is huge, approximately 172 kb in size. KS has a variable clinical course, ranging from minimal disease presenting as an incidental finding to a rapidly progressing neoplasm that can result in significant morbidity and mortality, depending on the specific site of involvement.

In latency, the KSHV genome persists as a circular episome in the nucleus of the host cell and only a few viral genes are expressed. The asterisk represents the identified viral genes that are involved in regulating the activity of DNMTs. This proposed volume will attempt to review and address the major gaps in current knowledge in DNA viruses as well as RNA viruses bringing a historical perspective of where studies began to a more recent molecular approach and vaccine successes in tumor viruses. Such cancers contained SV40 DNA, which was mostly detected by PCR [30–32]. Government. Multiple studies using this type of analysis clearly demonstrated that the EBV genome in many of the EBV-associated tumors, such as BL [26], NPC [23], and HD [11], is clonal in nature, strongly suggesting that these tumors developed from a single progenitor cell that was already infected with EBV, lending further support to the concept that EBV may be causally related to the genesis of many of these tumors.