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Journal of Virology Jun 2023Oncogenic virus infections are estimated to cause ~15% of all cancers. Two prevalent human oncogenic viruses are members of the gammaherpesvirus family: Epstein-Barr...
Oncogenic virus infections are estimated to cause ~15% of all cancers. Two prevalent human oncogenic viruses are members of the gammaherpesvirus family: Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV). We use murine herpesvirus 68 (MHV-68), which shares significant homology with KSHV and EBV, as a model system to study gammaherpesvirus lytic replication. Viruses implement distinct metabolic programs to support their life cycle, such as increasing the supply of lipids, amino acids, and nucleotide materials necessary to replicate. Our data define the global changes in the host cell metabolome and lipidome during gammaherpesvirus lytic replication. Our metabolomics analysis found that MHV-68 lytic infection induces glycolysis, glutaminolysis, lipid metabolism, and nucleotide metabolism. We additionally observed an increase in glutamine consumption and glutamine dehydrogenase protein expression. While both glucose and glutamine starvation of host cells decreased viral titers, glutamine starvation led to a greater loss in virion production. Our lipidomics analysis revealed a peak in triacylglycerides early during infection and an increase in free fatty acids and diacylglyceride later in the viral life cycle. Furthermore, we observed an increase in the protein expression of multiple lipogenic enzymes during infection. Interestingly, pharmacological inhibitors of glycolysis or lipogenesis resulted in decreased infectious virus production. Taken together, these results illustrate the global alterations in host cell metabolism during lytic gammaherpesvirus infection, establish essential pathways for viral production, and recommend targeted mechanisms to block viral spread and treat viral induced tumors. Viruses are intracellular parasites which lack their own metabolism, so they must hijack host cell metabolic machinery in order to increase the production of energy, proteins, fats, and genetic material necessary to replicate. Using murine herpesvirus 68 (MHV-68) as a model system to understand how similar human gammaherpesviruses cause cancer, we profiled the metabolic changes that occur during lytic MHV-68 infection and replication. We found that MHV-68 infection of host cells increases glucose, glutamine, lipid, and nucleotide metabolic pathways. We also showed inhibition or starvation of glucose, glutamine, or lipid metabolic pathways results in an inhibition of virus production. Ultimately, targeting changes in host cell metabolism due to viral infection can be used to treat gammaherpesvirus-induced cancers and infections in humans.
Topics: Animals; Mice; Glucose; Glutamine; Host Microbial Interactions; Lipidomics; Metabolome; Nucleotides; Rhadinovirus; Virus Replication; Fatty Acids; Herpesviridae Infections
PubMed: 37191529
DOI: 10.1128/jvi.00506-23 -
British Journal of Cancer Feb 2005We investigated a series of 122 cases of small cell lung carcinomas and non-small cell lung carcinomas for the presence of several viruses that are known to be oncogenic...
We investigated a series of 122 cases of small cell lung carcinomas and non-small cell lung carcinomas for the presence of several viruses that are known to be oncogenic in humans. Thus, viral genomes (DNA) and/or RNA transcripts and/or proteins of human papillomaviruses (HPV) 16, 18, 31, 33, 51, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), human cytomegalovirus (HCMV) and simian virus 40 (SV40) were investigated on tissue sections (prepared in tissue microarrays) with different techniques of immunohistochemistry and in situ hybridisation. None of the cases displayed a single positive tumour cell for all the viruses tested whatever the technique applied. Of note, in five cases of tumours with lymphoid infiltrates, we detected scattered EBV (EBER)-positive bystander lymphocytes. In three cases, a faint nuclear staining was found with the anti-latent nuclear antigen/LANA1 (HHV-8) antibody. These cases were checked by PCR with two sets of primers (orf 26 and orf 75) and remained negative for this latter virus. Taken together, our data strongly suggest that the conventional human oncogenic viruses (HPV, EBV, HCMV, HHV-8 and SV40) are unlikely to play some role in the development of lung carcinomas..
Topics: Adenocarcinoma; Antibodies, Viral; Carcinoid Tumor; Carcinoma, Large Cell; Carcinoma, Neuroendocrine; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cytomegalovirus; DNA, Viral; Genome, Viral; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Immunohistochemistry; In Situ Hybridization; Lung Neoplasms; Oncogenic Viruses; Papillomaviridae; Polymerase Chain Reaction; RNA, Viral; Simian virus 40; Viral Proteins
PubMed: 15700034
DOI: 10.1038/sj.bjc.6602409 -
Journal of Cellular Physiology Aug 2008The two human herpesviruses that are causally associated with cancer are Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus (KSHV). Both are... (Review)
Review
The two human herpesviruses that are causally associated with cancer are Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus (KSHV). Both are lymphocryptoviruses that establish latency in B lymphocytes and persist for the lifetime of the host. EBV and KSHV are both linked to a variety of lymphomas. EBV is also a causative agent or cofactor in epithelial malignancies such as nasopharyngeal carcinoma whereas Kaposi's sarcoma is of endothelial cell origin. Both viruses encode a limited number of proteins during latent replication that are important for growth transformation and evasion of the immune system. In addition, they express noncoding RNAs during both latent and lytic infection. Many of these RNAs have been highly conserved during evolution and are expressed in a wide variety of clinical settings, suggesting their fundamental importance in the viral life cycle. The function of some of these RNAs such as the nuclear EBV EBER RNAs remains elusive although they are some of the most abundant transcripts produced by each virus. Both EBV and KSHV also have recently been shown to encode and express microRNAs. The study of these viral microRNAs is just beginning although several of their cellular and viral gene targets have been established. Viral microRNAs appear to be involved in both modulation of the immune response as well as oncogenesis. Because each target gene may have many microRNAs acting on its mRNA, and each microRNA may have more than one target, there are likely to be many new discoveries regarding the complex interactions of viral microRNAs and host cell genes.
Topics: Animals; Apoptosis; Cell Transformation, Viral; Gammaherpesvirinae; Gene Expression Regulation; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Neoplasms; Oncogenic Viruses; RNA, Untranslated; RNA, Viral; Tumor Virus Infections
PubMed: 18484093
DOI: 10.1002/jcp.21480 -
Postepy Biochemii Dec 2020Viral infections contribute to many cancers worldwide and represent a significant percentage of deaths. Oncogenic viruses include the Epstein-Barr virus, which is the... (Review)
Review
Viral infections contribute to many cancers worldwide and represent a significant percentage of deaths. Oncogenic viruses include the Epstein-Barr virus, which is the main cause of infectious mononucleosis and exhibits tropism towards B lymphocytes. Due to the presence of genes responsible for latency, it can contribute to many pathological conditions. Examples of this are high-fatal malignancies located in the stomach as well as in the head and neck. Moreover, this virus poses a serious threat to immunocompromised people, which is a significant problem nowadays due to the increasing number of patients undergoing immunosuppressive therapy. Particular attention in this case is lymphoproliferative disorders after transplantation, which are a malignant neoplasm associated with EBV infection. This review focuses on the role of the Epstein-Barr virus in selected cancers.
Topics: Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoproliferative Disorders; Neoplasms
PubMed: 33470071
DOI: 10.18388/pb.2020_364 -
British Medical Journal (Clinical... May 1987
Review
Topics: Humans; Neoplasms; Oncogenes; Oncogenic Viruses
PubMed: 3109601
DOI: 10.1136/bmj.294.6582.1246 -
FEBS Letters Oct 2011Evidence over the last two decades from a number of disciplines has solidified some fundamental concepts in metastasis, a major contributor to cancer associated deaths.... (Review)
Review
Evidence over the last two decades from a number of disciplines has solidified some fundamental concepts in metastasis, a major contributor to cancer associated deaths. However, significant advances have been made in controlling this critical cellular process by focusing on targeted therapy. A key set of factors associated with this invasive phenotype is the nm23 family of over twenty metastasis-associated genes. Among the eight known isoforms, Nm23-H1 is the most studied potential anti-metastatic factor associated with human cancers. Importantly, a growing body of work has clearly suggested a critical role for Nm23-H1 in limiting tumor cell motility and progression induced by several tumor viruses, including Epstein-Barr virus (EBV), Kaposi's sarcoma associated herpes virus (KSHV) and human papilloma virus (HPV). A more in depth understanding of the interactions between tumor viruses encoded antigens and Nm23-H1 will facilitate the elucidation of underlying mechanism(s) which contribute to virus-associated cancers. Here, we review recent studies to explore the molecular links between human oncogenic viruses and progression of metastasis, in particular the deregulation of Nm23-H1 mediated suppression.
Topics: Animals; Antigens, Neoplasm; Antigens, Viral; Cell Movement; Humans; NM23 Nucleoside Diphosphate Kinases; Neoplasm Metastasis; Oncogenic Viruses; Tumor Suppressor Proteins; Tumor Virus Infections
PubMed: 21846466
DOI: 10.1016/j.febslet.2011.08.007 -
Journal of Clinical Pathology Feb 1984
Topics: Animals; Cell Division; Child; Humans; Interferon Inducers; Interferons; Neoplasms; Oncogenic Viruses; T-Lymphocytes; Virus Diseases; Viruses
PubMed: 6198337
DOI: 10.1136/jcp.37.2.109 -
European Cytokine Network 2001The outcome of a viral infection ranges from benign to fatal with the clinical pictures being very diverse. This is largely due to the virus-cell interactions that occur... (Review)
Review
The outcome of a viral infection ranges from benign to fatal with the clinical pictures being very diverse. This is largely due to the virus-cell interactions that occur in the infected organism. Rapidly after infection, cells initiate a first line of defense against the virus. The cells sense viruses through several mechanisms. Among these the ability to respond to accumulation of double-stranded RNA has been particularly well studied and seems to be of importance. On the other hand, the close co-existence of virus and host has allowed viruses to develop mechanisms to down-modulate the initial reaction or to exploit this proinflammatory response in its own advance. This review describes how virus infections affect cellular signal transduction and the mechanisms through which certain viruses modulate this response to dampen the immune response or prevent cell death.
Topics: Animals; Cell Transformation, Viral; Cells; Cytokines; Humans; Inflammation; NF-kappa B; Neoplasms; Oncogenic Viruses; Signal Transduction; Tumor Virus Infections; Viral Matrix Proteins; Virus Diseases; Viruses
PubMed: 11566618
DOI: No ID Found -
Open Biology Mar 2021Infections cause 13% of all cancers globally, and DNA tumour viruses account for almost 60% of these cancers. All viruses are obligate intracellular parasites and hijack... (Review)
Review
Infections cause 13% of all cancers globally, and DNA tumour viruses account for almost 60% of these cancers. All viruses are obligate intracellular parasites and hijack host cell functions to replicate and complete their life cycles to produce progeny virions. While many aspects of viral manipulation of host cells have been studied, how DNA tumour viruses manipulate host cell metabolism and whether metabolic alterations in the virus life cycle contribute to carcinogenesis are not well understood. In this review, we compare the differences in central carbon and fatty acid metabolism in host cells following infection, oncogenic transformation, and virus-driven cancer of DNA tumour viruses including: Epstein-Barr virus, hepatitis B virus, human papillomavirus, Kaposi's sarcoma-associated herpesvirus and Merkel cell polyomavirus.
Topics: Animals; Carbohydrate Metabolism; Humans; Lipid Metabolism; Neoplasms; Oncogenic Viruses
PubMed: 33653084
DOI: 10.1098/rsob.210004 -
The Journal of Experimental Medicine Nov 1964Electron microscope study of thymuses of both conventional and germ-free mice has revealed the presence of typical virus particles associated with the thymic lymphocytes...
Electron microscope study of thymuses of both conventional and germ-free mice has revealed the presence of typical virus particles associated with the thymic lymphocytes or with the thymic epithelial cells. The particles resemble those associated with several murine leukemias and their viral nature seems convincingly substantiated by morphological observation. Germ-free mice are therefore not virus-free. The biological significance of these particles is still unknown and we can only speculate as to the possible relationship of these particles to the incidence of "spontaneous" leukemia, to the lymphocytosis stimulating factor of Metcalf, and to the numerous latent viral infections of laboratory mice.
Topics: Animals; Breast Neoplasms; Electrons; Germ-Free Life; Humans; Leukemia Virus, Murine; Leukemia, Experimental; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Mice; Microscopy; Microscopy, Electron; Oncogenic Viruses; Research; Thymus Gland; Virion
PubMed: 14247725
DOI: 10.1084/jem.120.5.857