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Current Opinion in Virology Dec 2019Oncogenic viruses, like all viruses, relies on host metabolism to provide the metabolites and energy needed for virus replication. Many DNA tumor viruses and... (Review)
Review
Oncogenic viruses, like all viruses, relies on host metabolism to provide the metabolites and energy needed for virus replication. Many DNA tumor viruses and retroviruses will reprogram metabolism during infection. Additionally, some viral oncogenes may alter metabolism independent of virus replication. Virus infection and cancer development share many similarities regarding metabolic reprogramming as both processes demand increased metabolic activity to produce biomass: cell proliferation in the case of cancer and virion production in the case of infection. This review discusses the parallels in metabolic reprogramming between human oncogenic viruses and oncogenesis.
Topics: Biomass; Carcinogenesis; Cell Proliferation; Cellular Reprogramming; Hepacivirus; Hepatitis B virus; Herpesviridae; Humans; Merkel cell polyomavirus; Metabolic Networks and Pathways; Neoplasms; Oncogenic Viruses; Papillomaviridae; Retroviridae; Virion; Virus Replication
PubMed: 31766001
DOI: 10.1016/j.coviro.2019.11.002 -
The Chemokine System in Oncogenic Pathways Driven by Viruses: Perspectives for Cancer Immunotherapy.Cancers Feb 2022Chemokines interact with glycosaminoglycans of the extracellular matrix and activate heptahelical cellular receptors that mainly consist of G Protein-Coupled Receptors... (Review)
Review
Chemokines interact with glycosaminoglycans of the extracellular matrix and activate heptahelical cellular receptors that mainly consist of G Protein-Coupled Receptors and a few atypical receptors also with decoy activity. They are well-described targets of oncogenic pathways and key players in cancer development, invasiveness, and metastasis acting both at the level of cancer cells and cells of the tumor microenvironment. Hence, they can regulate cancer cell proliferation and survival and promote immune or endothelial cell migration into the tumor microenvironment. Additionally, oncogenic viruses display the potential of jeopardizing the chemokine system by encoding mimics of chemokines and receptors as well as several products such as oncogenic proteins or microRNAs that deregulate their human host transcriptome. Conversely, the chemokine system participates in the host responses that control the virus life cycle, knowing that most oncoviruses establish asymptomatic latent infections. Therefore, the deregulated expression and function of chemokines and receptors as a consequence of acquired or inherited mutations could bias oncovirus infection toward pro-oncogenic pathways. We here review these different processes and discuss the anticancer therapeutic potential of targeting chemokine availability or receptor activation, from signaling to decoy-associated functions, in combination with immunotherapies.
PubMed: 35159113
DOI: 10.3390/cancers14030848 -
Emerging Microbes & Infections Dec 2023Epstein-Barr virus (EBV) is the first reported human oncogenic virus and infects more than 95% of the human population worldwide. EBV latent infection in B lymphocytes...
Epstein-Barr virus (EBV) is the first reported human oncogenic virus and infects more than 95% of the human population worldwide. EBV latent infection in B lymphocytes is essential for viral persistence. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into B cells. The C-type lectin domain (CTLD) of gp42 plays a key role in receptor binding and is the major target of neutralizing antibodies. Here, we isolated two rabbit antibodies, 1A7 and 6G7, targeting gp42 CTLD with potent neutralizing activity against B cell infection. Antibody 6G7 efficiently protects humanized mice from lethal EBV challenge and EBV-induced lymphoma. Neutralizing epitopes targeted by antibodies 1A7 and 6G7 are distinct and novel. Antibody 6G7 blocks gp42 binding to B cell surface and both 1A7 and 6G7 inhibit membrane fusion with B cells. Furthermore, 1A7- and 6G7-like antibodies in immunized sera are major contributors to B cell neutralization. This study demonstrates that anti-gp42 neutralizing antibodies are effective in inhibiting EBV infection and sheds light on the design of gp42-based vaccines and therapeutics.
Topics: Rabbits; Humans; Animals; Mice; Herpesvirus 4, Human; Antibodies, Neutralizing; Epstein-Barr Virus Infections; Membrane Glycoproteins; Viral Proteins; Epitopes
PubMed: 37542379
DOI: 10.1080/22221751.2023.2245920 -
Viruses Dec 2019Viral lymphomagenesis induced by infection with oncogenic viruses, such as Kaposi's sarcoma associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and human T-cell... (Review)
Review
Viral lymphomagenesis induced by infection with oncogenic viruses, such as Kaposi's sarcoma associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and human T-cell leukemia virus (HTLV-1), represents a group of aggressive malignancies with a diverse range of pathological features. Combined chemotherapy remains the standard of care for these virus-associated lymphomas; however, frequent chemoresistance is a barrier to achieving successful long-term disease-free survival. There is increasing evidence that indicates virus-associated lymphomas display more resistance to cytotoxic chemotherapeutic agents than that observed in solid tumors. Although the tumor microenvironment and genetic changes, such as key oncogene mutations, are closely related to chemoresistance, some studies demonstrate that the components of oncogenic viruses themselves play pivotal roles in the multidrug chemoresistance of lymphoma cells. In this review, we summarize recent advances in the understanding of the mechanisms through which oncogenic viruses mediate lymphoma cell chemoresistance, with a particular focus on KSHV and EBV, two major oncogenic viruses. We also discuss the current challenges to overcome these obstacles in the treatment of virus-associated lymphomas.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Drug Resistance, Neoplasm; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoma; Oncogenic Viruses; Tumor Virus Infections
PubMed: 31888174
DOI: 10.3390/v11121161 -
Current Opinion in Virology Aug 2019Although bacterial dysbiosis has been previously associated with carcinogenesis and HIV infection, the impact of the virome and these disease states has been less well... (Review)
Review
Although bacterial dysbiosis has been previously associated with carcinogenesis and HIV infection, the impact of the virome and these disease states has been less well studied. In this review, we will summarize what is known about the interplay between both the bacterial and the viral components of the microbiome on cancer and HIV pathogenesis. Bacterial dysbiosis has been associated with carcinogenesis such as colorectal cancer (CRC), hepatocellular carcinoma (HCC), lung cancer, breast cancer, and gastric cancer. The dysbiotic pathogenesis may be species-based or community-based and can have varying mechanisms of carcinogenesis. The human virome was also associated with certain cancers. Viruses, such as cytomegalovirus (CMV), Human herpesvirus 8 (HHV-8), human papilloma virus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Epstein-Barr virus (EBV), all had associations with cancers. It was also reported that an altered bacteriophage community may lead to carcinogenesis by allowing opportunistic, oncogenic bacteria to proliferate in a gastrointestinal biofilm. This mechanism shows the importance of analyzing the bacteriome and the virome concurrently as their interactions can provide insight into new mechanisms in the pathogenesis of not only cancer, but other diseases as well. The enteric bacteriome was shown to be distinctly altered in immunocompromised HIV-infected individuals, and highly active antiretroviral therapy (HAART) was shown to at least partially reverse the alterations that HIV causes in the bacteriome. Studies have shown that the progression to HIV is associated with changes in the plasma concentration of commensal viruses. HIV also acts synergistically with multiple other viruses, such as HPV, EBV, varicella zoster virus (VZV), and HHV-8. Although it has been shown that HIV infection leads to enteric virome expansion in humans, most of the research on HIV's effect on the virome was conducted in non-human primates, and there is a lack of research on the effect of HAART on the virome. Virome-wide analysis is necessary for identifying novel viral etiologies. There is currently a wealth of information on the bacteriome and its associations with cancer and HIV, but more research should be conducted on the virome's associations and reaction to HAART as well as the bacteriome-virome interactions that may play a major role in pathogenesis and recovery.
Topics: Antiretroviral Therapy, Highly Active; Bacteria; Bacteriophages; Carcinoma, Hepatocellular; Cytomegalovirus; DNA, Viral; Dysbiosis; HIV Infections; Hepatitis B virus; Herpesvirus 4, Human; Herpesvirus 8, Human; Host Microbial Interactions; Humans; Liver Neoplasms; Microbial Interactions; Microbiota; Neoplasms; Virus Diseases; Viruses
PubMed: 31177014
DOI: 10.1016/j.coviro.2019.05.007 -
Biochimica Et Biophysica Acta. Reviews... May 2022Viruses lack essential living system, so they must hijack host cell metabolism for its survival and reproduction. Interestingly, the metabolic reprogramming induced by... (Review)
Review
Viruses lack essential living system, so they must hijack host cell metabolism for its survival and reproduction. Interestingly, the metabolic reprogramming induced by oncovirus is critical for the malignant transformation. Amino acid can supply the source of nitrogen and carbon for biosynthesis or fulfill the energy requirement for the rapid growth of tumor cells. Amino acid metabolism caused by oncogenic viral infection often mirrors metabolic changes observed in cancer cells, such as glutamine addiction, asparagine dependence, arginine auxotrophy and active serine/ proline metabolism. In this review, we describe amino acid metabolism reprogramming in tumors. We also discuss how oncogenic viruses hijack amino acid metabolism in the stress status. Further research on the metabolic profile of virus-related cancers will not only provide new targets for tumor prevention and treatment, but novel diagnostic and therapeutic strategies as well.
Topics: Amino Acids; Glutamine; Humans; Neoplasms; Oncogenic Viruses
PubMed: 35314213
DOI: 10.1016/j.bbcan.2022.188724 -
Current Opinion in Virology Dec 2019Human cytomegalovirus (HCMV) gene products are present in multiple human malignancies, often in specific association with tumor cells and tumor vasculature. Emerging... (Review)
Review
Human cytomegalovirus (HCMV) gene products are present in multiple human malignancies, often in specific association with tumor cells and tumor vasculature. Emerging evidence from human and mouse models of CMV infection in cancer indicate that CMV can transform epithelial cells, promote epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial (MET) in tumor cells, promote tumor angiogenesis and proliferation and incapacitate the host anti-CMV immune response. This review will discuss the increasing role of HCMV in human cancer by demonstrating how HCMV is well suited for impacting major themes in oncogenesis including initiation, promotion, progression, metastasis and immune evasion. What emerges is a picture of an extremely versatile pathogen that may play a significant role in human cancer progression and death.
Topics: Animals; Carcinogenesis; Cell Proliferation; Cytomegalovirus; Cytomegalovirus Infections; Epithelial Cells; Epithelial-Mesenchymal Transition; Humans; Mice; Neoplasm Metastasis; Neoplasms; Oncogenic Viruses
PubMed: 31525538
DOI: 10.1016/j.coviro.2019.08.003 -
Tumour Virus Research Dec 2022Human tumor viruses cause various human cancers that account for at least 15% of the global cancer burden. Among the currently identified human tumor viruses, two are... (Review)
Review
Human tumor viruses cause various human cancers that account for at least 15% of the global cancer burden. Among the currently identified human tumor viruses, two are small DNA tumor viruses: human papillomaviruses (HPVs) and Merkel cell polyomavirus (MCPyV). The study of small DNA tumor viruses (adenoviruses, polyomaviruses, and papillomaviruses) has facilitated several significant biological discoveries and established some of the first animal models of virus-associated cancers. The development and use of preclinical in vivo models to study HPVs and MCPyV and their role in human cancer is the focus of this review. Important considerations in the design of animal models of small DNA tumor virus infection and disease, including host range, cell tropism, choice of virus isolates, and the ability to recapitulate human disease, are presented. The types of infection-based and transgenic model strategies that are used to study HPVs and MCPyV, including their strengths and limitations, are also discussed. An overview of the current models that exist to study HPV and MCPyV infection and neoplastic disease are highlighted. These comparative models provide valuable platforms to study various aspects of virus-associated human disease and will continue to expand knowledge of human tumor viruses and their relationship with their hosts.
Topics: Animals; Humans; Merkel cell polyomavirus; Polyomavirus Infections; Tumor Virus Infections; Neoplasms; Polyomavirus; Oncogenic Viruses
PubMed: 35636683
DOI: 10.1016/j.tvr.2022.200239 -
Cancer Informatics 2023This review discusses the possible involvement of infections-associated cancers in humans, with virus infections contributing 15% to 20% of total cancer cases in humans.... (Review)
Review
This review discusses the possible involvement of infections-associated cancers in humans, with virus infections contributing 15% to 20% of total cancer cases in humans. DNA virus encoded proteins interact with host cellular signaling pathways and control proliferation, cell death and genomic integrity viral oncoproteins are known to bind cellular Deubiquitinates (DUBs) such as cyclindromatosis tumor suppressor, ubiquitin-specific proteases 7, 11, 15 and 20, and A-20 to improve their intracellular stability and cellular signaling pathways and finally transformation. Human papillomaviruses (cervical carcinoma, oral cancer and laryngeal cancer); human polyomaviruses (mesotheliomas, brain tumors); Epstein-Barr virus (B-cell lymphoproliferative diseases and nasopharyngeal carcinoma); Kaposi's Sarcoma Herpesvirus (Kaposi's Sarcoma and primary effusion lymphomas); hepatitis B (hepatocellular carcinoma (HCC)) cause up to 20% of malignancies around the world.
PubMed: 37363356
DOI: 10.1177/11769351231154186 -
Current Opinion in Oncology Mar 2020This review is an update of the recent findings on pathophysiology of Kaposi sarcoma, the role of HHV-8 in Kaposi sarcoma pathogenesis and to summarize the recent... (Review)
Review
PURPOSE OF REVIEW
This review is an update of the recent findings on pathophysiology of Kaposi sarcoma, the role of HHV-8 in Kaposi sarcoma pathogenesis and to summarize the recent advances in the treatment of Kaposi sarcoma and the role of immunity to control the disease.
RECENT FINDINGS
The causal agent of Kaposi sarcoma is HHV-8 and the mechanism by which HHV-8 drives the tumor development is unique. HHV-8 is not a classic oncogenic virus and the disease is an opportunistic tumor responding to immune restoration when it is possible.
SUMMARY
Five epidemiologic types of Kaposi are recognized and HHV-8 is associated to all epidemiologic forms of Kaposi. HHV-8 is a virus favoring both angiogenesis and cellular proliferation, which are the two main histological features of Kaposi sarcoma. Although in many cases, treatment of Kaposi sarcoma is not necessary, specific chemotherapy, immunomodulation and immune stimulation are the tools for treating Kaposi sarcoma. Monochemotherapy has been shown to be as efficient as polychemotherapy and less toxic. Immune checkpoint inhibitors gave some promising results, which should be confirmed by prospective studies.
Topics: Carcinogenesis; Herpesviridae Infections; Herpesvirus 8, Human; Humans; Randomized Controlled Trials as Topic; Sarcoma, Kaposi
PubMed: 31815777
DOI: 10.1097/CCO.0000000000000601