See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/281306129 Oncoviruses: An overview of oncogenic and oncolytic viruses Article in Oncobiology and Targets · January 2015 DOI: 10.4103/2395-4469.163581 CITATIONS READS 0 185 3 authors, including: Monal Yuwanati Shubhangi Mhaske People's College of Dental Sciences & Research Centre, Bhopal, India Peoples University 33 PUBLICATIONS 151 CITATIONS 33 PUBLICATIONS 149 CITATIONS SEE PROFILE SEE PROFILE Some of the authors of this publication are also working on these related projects: Publication View project All content following this page was uploaded by Monal Yuwanati on 16 August 2018. The user has requested enhancement of the downloaded file. [Downloaded free from http://www.oncotargets.com on Sunday, August 30, 2015, IP: 122.168.164.199] Review Article Access this article online Oncoviruses: An overview of oncogenic Quick Response Code: and oncolytic viruses Shubhangi Mhaske, Monal Yuwanati, Nikita Bhatnagar Abstract: Website: www.oncotargets.com The knowledge of tumor biology has created the potential to develop and understand the mystery of the oncogenic and oncolytic viruses. The facts with viral oncogenesis have surprised the mankind by the development of DOI: oncolytic therapy by the viruses themselves. The objective of this paper was to overview the concept of 10.4103/2395-4469.163581 oncogenesis and oncolysis by the deoxyribonucleic acid and ribonucleic acid viruses. In spite of the fact that viruses indulge in causing cancers, advances are also being made in the field of oncolysis by viral therapy. Although in its infancy, oncolytic viral therapy has already produced some notable successes. The viruses are selectively modified with incorporation and deletion of genes required for them to be tumor‑specific. These modified oncolytic viruses are also used in oncolysis of oral cancers by administrating them either intratumorally or systemically. With diverse nature of tumors, some being radio‑resistant and another chemo‑resistant, the notion of oncolytic viruses being used as adjunct to the conventional treatment modalities is of great significant value. This paper presents an overview of the various aspects of oncogenic and oncolytic viruses in a concise manner with discussion about the mode of administration of oncolytic viruses, their scope and their future potential in treatment of oral cancers. Key words: Adenovirus, Epstein‑Barr virus, herpesvirus, oncogenic virus, oncolytic virus, oral cancer, tumor suppressor genes Introduction are governed by complex regulatory networks and are surveyed by mechanisms that certify that Oncogenic viruses abnormal cells are removed from the proliferative The concept of cancer etiology seems to be pool. OV inactivate these surveillance incomplete without mentioning the indispensible mechanisms that would normally recognize role of viruses. There were 10.9 million new cases, and put out such abnormal cells. Viruses are 6.7 million deaths, and 24.6 million persons alive accepted as causative factor for human cancer. with cancer (within 3 years of diagnosis).[1] As Different guidelines had been proposed to aid estimated, 15% of all human cancers worldwide in establishing a causal relationship between may be attributed to viruses, expressing a viruses and cancers [Table 3]. Although few of significant cancer burden worldwide.[2] Much the guidelines are not applicable for all viruses, of what is known today about cancer and its still they are quite useful. related genes responsible for cancer causation Department of can be attributed to the studies on oncogenic Mechanism for Viral Oncogenesis Oral Pathology deoxyribonucleic acid (DNA) and ribonucleic [3] and Microbiology, acid (RNA) viruses. Epstein‑Barr virus (EBV), The characteristic feature of cancer cell is loss [4] Peoples Dental Human Papillomavirus (HPV), hepatitis B of growth control by escaping the checkpoint [5] [6] Academy, Bhopal, virus, and human herpesvirus‑8 are the during normal cell cycle. The retinoblastoma (Rb Madhya Pradesh, India documented DNA viruses contributing to gene) and p53 genes are main tumor suppressor the carcinogenesis. Human T lymphotropic genes involved in checkpoints. Rb gene acts as virus type I (HTLV type I)[7] and hepatitis C an ON‑OFF switch for the cell cycle. This gene Address for viruses (HCV)[8] are the RNA viruses that are brings about its action by forming tight inactive correspondence: considered to be oncogenic viruses (OV).[9] The OV complex with the transcriptional factor (E2F) Dr. Monal Yuwanati, are enlisted in Table 1 with their tumor‑specific which is thus not available for progression of Department of Oral Pathology, Peoples types. The various milestones in the discovery of cell cycle. The main role of p53 in a normal cell Dental Academy, Peoples various OV have been enlisted in Table 2. cycle is of surveillance and triggering check point Campus, Bhanpur, controls that slow down or stops the cell cycle. It Bhopal - 462 037, Viruses being obligatory intracellular parasites mediated its action by transcriptional activation Madhya Pradesh, India. encode proteins that reprogram host cellular of p21 (member of Cip/Kip family along with E-mail: monal9817@ signaling pathways. This in turn controls p27 and p57) at the G1/S checkpoint of the gmail.com the proliferation and differentiation of cells, normal cell cycle. Alteration in these normal Submission: 26-03-2015 cell death, integrity of the genome and also pathways by OV (which act as initiators) may Accepted: 17-05-2015 recognition by immune system. These processes lead to uncontrolled proliferation of the tumor 4 Oncobiology and Targets - Vol 2 | Issue 1 | Jan-Feb 2015 [Downloaded free from http://www.oncotargets.com on Sunday, August 30, 2015, IP: 122.168.164.199] Mhaske, et al.: Oncogenic and oncolytic viruses cells. This transformation of the normal cells into cancer cells Table 2: Important milestones in history of OV usually occurs with two distinct phases of Initiation and Year Discoveries/contributions/key events Promotion. The tumor suppressor genes encode proteins that 1903 Advanced the hypothesis of the infectious nature of restrain cell growth and are part of the negative control of cell cancers cycle regulation. The mutation in these genes primarily leads to 1907 Discovery of HPV the uncontrolled proliferation of the cells. The Rb gene encodes 1908 Identification and discovery of avian leukemia virus a 928‑amino acid phosphoprotein, Rb which is phosphorylated 1911 Discovery of avian RSV [11] by cyclin‑dependent kinase. This phosphorylation leads to 1933 CRPV discovered the release of binded E2F and permits the G1 to S transition 1935 Induction of carcinoma in domestic rabbits by and thus the replication occurs. In case of p53 gene, there is CRPV‑first DNA tumor virus expression of protein (p21) that inhibits the cdc2 kinase. This 1936 Mouse mammary tumor virus‑discovered a milk basically prevents the premature entry of the cell into the S factor, which they considered to be responsible for phase of cell cycle. However, if the cell lacks the functional p53 the mammary adenocarcinoma of the mouse protein due to damage of wild type of p53 gene, there may be 1947 A virus identified as the causing agent of Rous sarcoma [12] progress toward the transformation of the cell. The mutated 1951 Murine leukemia virus discovered genes are now referred to as oncogenes those codes for a protein 1953 Mouse polyomavirus discovered that can potentially transform normal cell into malignant cell 1953‑54 Human adenovirus discovered if these oncogenes are transmitted by viruses they are called as viral oncogenes. 1961 SV40 discovered by Eddy at NIH, and Hillman and Sweet at Merck laboratory as a rhesus macaque virus contaminating cells used to make of Salk and Various viruses mainly responsible for the development of Sabin polio vaccines oral cancers with their mechanisms of tumorigenesis have 1964 The initial discovery of herpes‑type viral been described. These mechanisms vary for both DNA and particles (EBV) later on linked to specific human RNA viruses. malignant disease was made 1966 Was awarded the Noble Prize for his pioneering Deoxyribonucleic Acid Oncogenic Viruses work in animal tumor viruses 1967‑68 HBV discovered Human papillomavirus 1970 Reverse transcriptase discovered In case of Papillomaviruses, there are two oncogenes E6 1974‑84 Link found between HPV infection and cervical and E7. These are associated with HPV types 16 and 18 cancer and are able to mutate large set of cellular genes. In case of 1975 Link between HBV infection and HCC Papillomaviruses, the two oncogenes, E6 and E7 genes of 1976 Cellular origin of retroviral oncogenes discovered HPV types 16 and 18, modify a large set of cellular genes. 1976 HBV vaccine developed – first cancer vaccine These oncogenes either functionally inactivate the cellular 1979 P53 tumor suppressor discovered genes or target them for degradation. They either change 1980 T‑lymphotropic retrovirus type I was discovered in 1981 1980 and linked to adult T‑cell leukemia Table 1: Virus‑associated tumors 1981 A firm link of HBV to liver cancer became apparent Viruses Tumor types from epidemiological studies was published EBV Burkitt’s lymphoma 1983 Starting in 1983 and 1984 novel types of anogenital Nasopharyngeal carcinoma 1984 papillomaviruses were isolated directly from cervical Lymphomas under cancer biopsies immunosuppression 1986 E2F discovered Hodgkin’s disease 1988‑89 Interaction