About 15-20% of human cancers worldwide have viral etiology. Seven human DNA and RNA viruses are accepted to be oncogenic viruses or oncoviruses and contribute to the development of various cancer ...types. Human oncoviruses have developed multiple molecular mechanisms to interfere with specific cellular pathways to promote viral replication and viral life cycle maintenance in the host. Despite the diversity of oncogenic viruses, they use similar strategies for cancer development. Viral oncoproteins and viral non-coding RNAs are the key factors that can affect multiple cellular processes on both genetic and epigenetic levels. Epigenetics research allows better understanding of the complex interplay between oncoviruses and the host cells. This review highlights the importance of epigenetic reprogramming for virus-induced carcinogenesis. Recent progress in the development of pharmacological tools for targeting epigenetic mechanisms opens new perspectives for modulation of virus/host interaction and intervention of virus-induced cancer. Several clinical trials have been carried out or are on-going involving epigenetic drugs not only as single therapeutic but also in combination with other targeted agents against various virus-induced cancers.
Human herpesviruses (HHVs) and human papillomavirus (HPV) are common in the general population and, in immunocompetent people, are mostly carried asymptomatically. However, once an individual becomes ...immunocompromised by age, illness or HIV infection these dormant viruses can manifest and produce disease. In HIV‐positive patients, there is an increased risk of disease caused by HHVs and HPV infections and cancers caused by the oncoviruses Epstein–Barr Virus, HHV‐8 and HPV. This workshop examined four questions regarding the viruses associated with oral cancers and disease in the HIV‐positive and ‐negative populations, the immune response, and biomarkers useful for accurate diagnostics of these infections and their sequalae. Each presenter identified a number of key areas where further research is required.
Viral Noncoding RNAs in Cancer Biology Li, Zhi; Fu, Shujun; Sun, Lun-Quan
Advances in experimental medicine and biology,
01/2016, Letnik:
927
Journal Article
Recenzirano
Over 12 % of all human cancers are caused by oncoviruses, primarily including Epstein-Barr virus (EBV), high-risk human papillomaviruses (HPVs), hepatitis B and C viruses (HBV and HCV, respectively), ...and Kaposi's sarcoma herpesvirus (KSHV). In addition to viral oncoproteins, a variety of noncoding RNAs (ncRNAs) produced by oncoviruses have been recognized as important cofactors that contribute to the oncogenic events. In this chapter, we will focus on the recent understanding of the long and short noncoding RNAs, as well as microRNAs of the viruses, and discuss their roles in the biology of multistep oncogenesis mediated by established human oncoviruses.
Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the ...approach fails to detect novel pathogens and remote variants not present in reference databases. We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances. We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples. Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants. Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified.
As the mechanisms leading to the persistence of hepatitis B virus (HBV) infection are poorly understood and as the histocompatibility leucocyte antigen (HLA)‐G is well described as a tolerogenic ...molecule, we evaluated HLA‐G expression in 74 specimens of HBV liver biopsies and in 10 specimens obtained from previously healthy cadaver liver donors. HBV specimens were reviewed and classified by the METAVIR score, and HLA‐G expression was assessed by immunohistochemistry. No HLA‐G expression was observed in control hepatocytes. In contrast, 57 (77%) of 74 HBV specimens showed soluble and membrane‐bound HLA‐G expression in hepatocytes, biliary epithelial cells or both. No associations between the intensity of HLA‐G expression and patient age or gender, HBeAg status, severity of liver fibrosis, and grade of histological findings were observed. Although significance was not reached (P = 0.180), patients exhibiting HLA‐G expression presented a higher median HBV DNA viral load (105 copies/mL) than those who did not express HLA‐G (103.7 copies/mL). These results indicate that HLA‐G is expressed in most cases of chronic HBV infection in all stages and may play a role in the persistency of HBV infection.
The study of tumor viruses paves the way for understanding the mechanisms of virus pathogenesis, including those involved in establishing infection and dissemination in the host tumor affecting ...immune-compromised patients. The processes ranging from viral infection to progressing malignancy are slow and usually insufficient for establishment of transformed cells that develop cancer in only a minority of infected subjects. Therefore, viral infection is usually not the only cause of cancer, and further environmental and host factors, may be implicated. HTLV-I, in particular, is considered as an oncovirus cause of lymphoproliferative disease such as adult T cell leukemia/lymphoma (ATL) and disturbs the immune responses which results in HTLV-I associated meylopathy/tropical spastic parapresis (HAM/TSP). HTLV-I infection causes ATL in a small proportion of infected subjects (2-5%) following a prolonged incubation period (15-30 years) despite a strong adaptive immune response against the virus. Overall, these conditions offer a prospect to study the molecular basis of tumorgenicity in mammalian cells. In this review, the oncogencity of HTLV-I is being considered as an oncovirus in context of ATL.
Eight percent of our DNA contains retroviruses that are millions of years old. Anna Marie Skalka explains how our evolving knowledge of these particles has advanced genetic engineering, gene delivery ...systems, and precision medicine. Retroviruses cause disease but also hold clues to prevention and treatment possibilities that are anything but retro.
There are three major types of human retroviruses, namely HIV, HTLV, and endogenous human retroviruses. This book presents the latest findings on the replication of these human retroviruses. This ...book is unique in that there has been no comparable book that integrates the findings from the three known classes of human retroviruses. Other books have focused on one of the three classes of human retroviruses individually.An accomplished international team of contributing authors have combined their expertise to provide cutting-edge findings in this important field. The book will be a valuable reference for students, researchers and medical professionals.
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