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Biochimica Et Biophysica Acta.... Oct 2020Oncogenic viruses are among the apparent causes of cancer-associated mortality. It was estimated that 12% to 15% of human malignancies are linked to oncoviruses....
Oncogenic viruses are among the apparent causes of cancer-associated mortality. It was estimated that 12% to 15% of human malignancies are linked to oncoviruses. Although modernist strategies and traditional genetic studies have defined host-pathogen interactions of the oncoviruses, their host functions which are critical for the establishment of infection still remain mysterious. However, over the last few years, it has become clear that infections hijack and modify cellular pathways for their benefit. In this context, we constructed the virus-host protein interaction networks of seven oncoviruses (EBV, HBV, HCV, HTLV-1, HHV8, HPV16, and HPV18), and revealed cellular pathways hijacking as a result of oncogenic virus infection. Several signaling pathways/processes such as TGF-β signaling, cell cycle, retinoblastoma tumor suppressor protein, and androgen receptor signaling were mutually targeted by viruses to induce oncogenesis. Besides, cellular pathways specific to a certain virus were detected. By this study, we believe that we improve the understanding of the molecular pathogenesis of viral oncogenesis and provide information in setting new targets for treatment, prognosis, and diagnosis.
Topics: Carcinogenesis; Host-Pathogen Interactions; Humans; Neoplasms; Oncogenic Viruses; Protein Interaction Mapping; Protein Interaction Maps; Signal Transduction; Viral Proteins
PubMed: 32574835
DOI: 10.1016/j.bbadis.2020.165885 -
Computers in Biology and Medicine Mar 2021Globally, ~20% of cancer malignancies are associated with virus infections. Lung cancer is the most prevalent cancer and has a 10% 5-year survival rate when diagnosed at...
Globally, ~20% of cancer malignancies are associated with virus infections. Lung cancer is the most prevalent cancer and has a 10% 5-year survival rate when diagnosed at stage IV. Cancer vaccines and oncolytic immunotherapy are promising treatment strategies for better clinical outcomes in advanced-stage cancer patients. Here, we used a reverse vaccinology approach to devise subunit vaccine candidates against lung cancer-causing oncogenic viruses. Protein components (945) from nine oncogenic virus species were systematically analyzed to identify epitope-based subunit vaccine candidates. Best vaccine candidates were identified based on their predicted ability to stimulate humoral and cell-mediated immunity and avoid self-tolerance. Using a rigorous integrative approach, we identified 125 best antigenic epitopes with predicted B-cell, T-cell, and/or MHC-binding capability and vaccine adjuvant potential. Thirty-two of these antigenic epitopes were predicted to have IL-4/IFN-gamma inducing potential and IL-10 non-inducing potential and were predicted to bind 15 MHC-type I and 49 MHC-type II alleles. All 32 epitopes were non-allergenic and 31 were non-toxic. The identified epitopes showed good conservancy and likely bind a broad class of human HLA alleles, indicating promiscuous potential. The majority of best antigenic epitopes were derived from Human papillomavirus and Epstein-Barr virus proteins. Of the 32 epitopes, 25 promiscuous epitopes were related to E1 and E6 envelope genes and were present in multiple viral strains/species, potentially providing heterologous immunity. Further validating our results, 38 antigenic epitopes were also present in the largest experimentally-validated epitope resource, Immune Epitope Database and Analysis Resource. We further narrowed the selection to 29 antigenic epitopes with the highest immunogenic/immune-boosting potential. These epitopes possess tremendous therapeutic potential as vaccines against lung cancer-causing viruses and should be validated in future experiments. All findings are available at https://webs.iiitd.edu.in/raghava/vlcvirus/.
Topics: Computational Biology; Epitopes, T-Lymphocyte; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lung Neoplasms; Oncogenic Viruses; Vaccines, Subunit
PubMed: 33465550
DOI: 10.1016/j.compbiomed.2021.104215 -
Srpski Arhiv Za Celokupno Lekarstvo 2005Oncogenic viruses trigger persistent infections, which can stimulate uncontrolled cell growth by inducing cell transformation. Different oncogenic viruses use different... (Review)
Review
Oncogenic viruses trigger persistent infections, which can stimulate uncontrolled cell growth by inducing cell transformation. Different oncogenic viruses use different mechanisms for infecting cells. Most oncogenic DNA viruses integrate transforming sets of genes into the host chromosome and encode proteins that bind and inactivate cell growth regulatory proteins, such as p53 and retinoblastoma gene product. Tumourous RNA viruses use different oncogenic mechanisms. Some of them encode oncogenic proteins that are almost identical to the cellular proteins involved in the control of cellular growth. The overproduction or altered function of these oncogenic materials stimulates cell growth. These RNA viruses can cause tumours rapidly. The second group of oncoviruses integrates their promoter sequences and viral enhancers near to the cellular growth-stimulating gene, initiating the transformation of the cell. The third group of RNA tumour viruses encodes a protein tax that transactivates the expression of cellular genes. Virus-induced malignant transformation of the cell represents the first step in the complex process of oncogenesis.
Topics: Cell Transformation, Neoplastic; Cell Transformation, Viral; Humans; Neoplasms; Oncogenic Viruses
PubMed: 16623266
DOI: 10.2298/sarh0508384c -
The British Journal of Dermatology 2015
Topics: Gene Expression Profiling; Humans; Mycosis Fungoides; Oncogenic Viruses; Sezary Syndrome; Skin Neoplasms; Tumor Virus Infections
PubMed: 25385510
DOI: 10.1111/bjd.13519 -
Lancet (London, England)
Topics: Herpesviridae; Humans; Oncogenic Viruses
PubMed: 2878280
DOI: No ID Found -
The New England Journal of Medicine Jul 2002
Topics: Genes, myc; Hepacivirus; Herpesvirus 4, Human; Herpesvirus 8, Human; Human T-lymphotropic virus 1; Humans; Lymphoma; Oncogenic Viruses
PubMed: 12110734
DOI: 10.1056/NEJMp020056 -
Deutsche Medizinische Wochenschrift... Mar 1965
Review
Topics: Animals; Avian Leukosis Virus; Avian Sarcoma Viruses; DNA; DNA, Neoplasm; Leukemia Virus, Murine; Mice; Neoplasms; Neoplasms, Experimental; Oncogenic Viruses; Polyomavirus; RNA; RNA, Neoplasm; Research; Rous sarcoma virus
PubMed: 14242205
DOI: 10.1055/s-0028-1111361 -
Oncogene Dec 2008The study of acute-transforming retroviruses and their oncogenes and of the multiple mechanisms deployed by DNA viruses to circumvent the growth-suppressive and... (Review)
Review
The study of acute-transforming retroviruses and their oncogenes and of the multiple mechanisms deployed by DNA viruses to circumvent the growth-suppressive and proapoptotic function of tumor suppressor genes has provided the foundation of our current understanding of cancer biology. 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. The relevance of viral infection to human cancer development has often been debated. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), human T-cell lymphotropic virus (HTLV-1) and Kaposi's associated sarcoma virus (KSHV) contribute to 10-15% of the cancers worldwide. Hence, the opportunity exists to fight cancer at the global scale by preventing the spread of these viruses, by the development and distribution of effective and safe antiviral vaccines, and by identifying their oncogenic mechanism. Here, we discuss the molecular events underlying the neoplastic potential of the human tumor-associated viruses, with emphasis on the enigmatic KSHV and its numerous virally hijacked proangiogenic, immune-evasive and tumor-promoting genes. The emerging information may facilitate the development of new molecular-targeted approaches to prevent and treat virally associated human malignancies.
Topics: Hepacivirus; Hepatitis B virus; Herpesvirus 4, Human; Herpesvirus 8, Human; Host-Pathogen Interactions; Human T-lymphotropic virus 1; Humans; Neoplasms; Oncogenic Viruses; Papillomaviridae; Tumor Virus Infections
PubMed: 19956178
DOI: 10.1038/onc.2009.351 -
The Journal of Experimental Medicine Aug 1979Murine teratocarcinoma stem cells are nonpermissive for productive infection by a variety of DNA (polyoma and SV40 virus) and RNA (murine leukemia and sarcoma virus)...
Murine teratocarcinoma stem cells are nonpermissive for productive infection by a variety of DNA (polyoma and SV40 virus) and RNA (murine leukemia and sarcoma virus) tumor viruses whereas differentiated murine cells derived from the stem cells are permissive for productive (or abortive in the case of SV40) infection by these same viruses. The block to productive infection by these oncogenic viruses is at a postpenetration step in the replication cycle of these viruses but the precise level of the block has not been established for any of these viruses. In this report we describe teratocarcinoma-derived stem and differentiated cell lines which should be especially useful in determining the level of the block to replication of ecotropic murine leukemia virus in murine teratocarcinoma stem cells. The stem cell line, OTT6050AF1 BrdU, which is completely nonpermissive to productive infection by Moloney murine leukemia virus and consists of 97% pluripotent stem cells, contains DNA copies of an RNA tumor virus which is indistinguishable from the N-tropic murine leukemia virus of AKR mice. The stem cells are negative for expression of viral reverse transcriptase, p30 and gp69/71 and no virus is found by XC plaque assay or other biological tests. Differentiated cells established from the same teratocarcinoma tumor are 100% positive for viral gp69/71, p30, and produce large amounts of reverse transcriptase activity and N-tropic virus as detected by biological assay. The virus isolated from the differentiated cells is closely related, if not identical to AKR N-tropic virus by nucleic acid hybridization studies and is thus not an endogenous virus of the 129 strain of mice. The teratocarcinoma tumor from which the cell lines were established had been carried in 129 mice and perhaps at some time in the mouse passage history the tumors were infected (nonproductively) with the N-tropic virus. Regardless of the origin of this viral DNA, the OTT6050A derived stem and differentiated cell lines should be extremely useful in defining in stem cells the step at which ecotropic murine leukemia virus replication is blocked.
Topics: Animals; Antigens, Neoplasm; Antigens, Viral; Cell Line; Genes, Viral; Mice; Neoplasms, Experimental; Nucleic Acid Hybridization; Oncogenic Viruses; Teratoma
PubMed: 458380
DOI: 10.1084/jem.150.2.392 -
The American Journal of Medicine Jan 1987For more than a century, medical investigators have sought to incriminate microorganisms in the cause of cancer. The first scientific evidence of such a relationship... (Review)
Review
For more than a century, medical investigators have sought to incriminate microorganisms in the cause of cancer. The first scientific evidence of such a relationship came in 1911, with the first successful induction of a tumor using a cell-free extract. Since that time, considerable data have accrued linking retroviruses, herpes viruses, the hepatitis B virus, papovaviruses, and adenoviruses to various malignant neoplasms. There is also increasing evidence that certain bacteria and parasites participate as cofactors in the development of some cancers. Although proof of cause-and-effect relationships has been difficult to obtain, there can be little doubt that microorganisms occasionally play pivotal roles in the origin of some cancers. Whether attempted intervention against these cancers is best directed against the oncogenic microorganisms themselves or against other environmental cofactors is not yet clear. Nevertheless, the successful application of tumor vaccines in the prevention of Marek's disease in chickens and in modifying the outcome of oncogenic herpesvirus infections in nonhuman primates offers hope of at least limited application of microbial vaccines in the prevention of human cancer.
Topics: Adenoviridae; Animals; Bacteria; Cocarcinogenesis; Hepatitis B virus; Herpesviridae; Humans; Neoplasms; Oncogenic Viruses; Papillomaviridae; Polyomaviridae; Retroviridae; Schistosoma
PubMed: 3541601
DOI: 10.1016/0002-9343(87)90381-0