scholarly journals The Role of Dendritic Cells in Immune Control and Vaccination against γ-Herpesviruses

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1125 ◽  
Author(s):  
Christian Münz
Keyword(s):  
Kaposi Sarcoma ◽  
Immune Control ◽  
Barr Virus ◽  
Persistent Infections ◽  
Cell Responses ◽  
Tumor Virus ◽  
Epstein Barr ◽  
Antigen Presenting ◽  
Adoptive Transfer Therapy

The two human oncogenic γ-herpesviruses, Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), are prototypic pathogens that are controlled by T cell responses. Despite their ubiquitous distribution, persistent infections and transforming potential, most carriers’ immune systems control them for life. Therefore, they serve as paradigms of how near-perfect cell-mediated immune control can be initiated and maintained for decades. Interestingly, EBV especially quite efficiently avoids dendritic cell (DC) activation, and little evidence exists that these most potent antigen-presenting cells of the human body are involved in the priming of immune control against this tumor virus. However, DCs can be harnessed therapeutically to expand virus-specific T cells for adoptive transfer therapy of patients with virus-associated malignancies and are also currently explored for vaccinations. Unfortunately, despite 55 and 25 years of research on EBV and KSHV, respectively, the priming of their immune control that belongs to the most robust and durable immune responses in humans still remains unclear.

scholarly journals Modification of EBV Associated Lymphomagenesis and Its Immune Control by Co-Infections and Genetics in Humanized Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Patrick Schuhmachers ◽  
Christian Münz
Keyword(s):  
Adult Population ◽  
Human Tumor ◽  
Kaposi Sarcoma ◽  
Humanized Mice ◽  
Immune Control ◽  
Barr Virus ◽  
Human B Cells ◽  
Tumor Virus ◽  
Epstein Barr ◽  
Potent Growth

Epstein Barr virus (EBV) is one of the most successful pathogens in humans with more than 95% of the human adult population persistently infected. EBV infects only humans and threatens these with its potent growth transforming ability that readily allows for immortalization of human B cells in culture. Accordingly, it is also found in around 1-2% of human tumors, primarily lymphomas and epithelial cell carcinomas. Fortunately, however, our immune system has learned to control this most transforming human tumor virus in most EBV carriers, and it requires modification of EBV associated lymphomagenesis and its immune control by either co-infections, such as malaria, Kaposi sarcoma associated herpesvirus (KSHV) and human immunodeficiency virus (HIV), or genetic predispositions for EBV positive tumors to emerge. Some of these can be modelled in humanized mice that, therefore, provide a valuable platform to test curative immunotherapies and prophylactic vaccines against these EBV associated pathologies.

scholarly journals Natural Killer Cell Responses during Human γ-Herpesvirus Infections

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 655
Author(s):  
Christian Münz
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Epstein Barr Virus ◽  
Nk Cell ◽  
Killer Cell ◽  
Kaposi Sarcoma ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Barr Virus ◽  
Cell Responses ◽  
Epstein Barr

Herpesviruses are main sculptors of natural killer (NK) cell repertoires. While the β-herpesvirus human cytomegalovirus (CMV) drives the accumulation of adaptive NKG2C-positive NK cells, the human γ-herpesvirus Epstein–Barr virus (EBV) expands early differentiated NKG2A-positive NK cells. While adaptive NK cells support adaptive immunity by antibody-dependent cellular cytotoxicity, NKG2A-positive NK cells seem to preferentially target lytic EBV replicating B cells. The importance of this restriction of EBV replication during γ-herpesvirus pathogenesis will be discussed. Furthermore, the modification of EBV-driven NK cell expansion by coinfections, including by the other human γ-herpesvirus Kaposi sarcoma-associated herpesvirus (KSHV), will be summarized.

scholarly journals Modification of EBV-Associated Pathologies and Immune Control by Coinfections

2021 ◽  
Vol 11 ◽  
Author(s):  
Christian Münz
Keyword(s):  
Adult Population ◽  
Kaposi Sarcoma ◽  
Human Immune System ◽  
Immune Control ◽  
Barr Virus ◽  
Human B Cells ◽  
Immunodeficiency Virus ◽  
Epstein Barr ◽  
Underlying Mechanisms

The oncogenic Epstein–Barr virus (EBV) persistently infects more than 95% of the human adult population. Even so it can readily transform human B cells after infection in vitro, it only rarely causes tumors in patients. A substantial proportion of the 1% of all human cancers that are associated with EBV occurs during coinfections, including those with the malaria parasite Plasmodium falciparum, the human immunodeficiency virus (HIV), and the also oncogenic and closely EBV-related Kaposi sarcoma-associated herpesvirus (KSHV). In this review, I will discuss how these infections interact with EBV, modify its immune control, and shape its tumorigenesis. The underlying mechanisms reveal new aspects of EBV-associated pathologies and point toward treatment possibilities for their prevention by the human immune system.

scholarly journals The Role of Lytic Infection for Lymphomagenesis of Human γ-Herpesviruses

2021 ◽  
Vol 11 ◽  
Author(s):  
Christian Münz
Keyword(s):  
Kaposi Sarcoma ◽  
Lytic Replication ◽  
Host Cells ◽  
Paradigm Change ◽  
Oncogenic Viruses ◽  
Lytic Gene ◽  
Barr Virus ◽  
Bona Fide ◽  
Epstein Barr

Epstein Barr virus (EBV) and Kaposi sarcoma associated herpesvirus (KSHV) are two oncogenic human γ-herpesviruses that are each associated with 1-2% of human tumors. They encode bona fide oncogenes that they express during latent infection to amplify their host cells and themselves within these. In contrast, lytic virus particle producing infection has been considered to destroy host cells and might be even induced to therapeutically eliminate EBV and KSHV associated tumors. However, it has become apparent in recent years that early lytic replication supports tumorigenesis by these two human oncogenic viruses. This review will discuss the evidence for this paradigm change and how lytic gene products might condition the microenvironment to facilitate EBV and KSHV associated tumorigenesis.

Are Viruses and Parasites Linked to Celiac Disease? A Question that Still has no Definite Answer

2019 ◽  
Vol 20 (14) ◽  
pp. 1181-1193 ◽  
Author(s):  
Aref Shariati ◽  
Hamid R. Aslani ◽  
Mohammad R.H. Shayesteh ◽  
Ali Taghipour ◽  
Ahmad Nasser ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Multiple Roles ◽  
Barr Virus ◽  
The People ◽  
Intestinal Infections ◽  
Inflammatory Bowel ◽  
Epstein Barr ◽  
Irritable Bowel ◽  
Related Proteins

Celiac Disease (CD) is a complex autoimmune enteropathy of the small intestine that commonly occurs in genetically predisposed individuals due to intake of gluten and related proteins. Gluten consumption, duration of breast-feeding, various infections, especially frequent intestinal infections, vaccinations and use of antibiotics can be linked to CD. It is predicted that it affects 1% of the global population and its incidence rate is increasing. Most of the people with the HLA-DQ2 or HLADQ8 are at a higher risk of developing this disease. The link between infections and autoimmune diseases has been very much considered in recent years. In several studies, we explained that pathogenic and non-pathogenic microorganisms might have multiple roles in initiation, exacerbation, and development of Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). In various studies, the relationship between infections caused by viruses, such as Epstein-Barr Virus (EBV), Rotavirus, Hepatitis C (HCV), Hepatitis B virus (HBV), Cytomegalovirus (CMV), and Influenza virus, and parasites including Giardia spp. and Toxoplasma gondii with CD has been raised. However, increasing evidence proposes that some of these microorganisms, especially helminths, can also have protective and even therapeutic roles in the CD process. Therefore, in order to determine the role of microorganisms in the process of this disease, we attempted to summarize the evidence suggesting the role of viral and parasitic agents in pathogenesis of CD.

scholarly journals Virus-Driven Carcinogenesis

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2625
Author(s):  
Yuichiro Hatano ◽  
Takayasu Ideta ◽  
Akihiro Hirata ◽  
Kayoko Hatano ◽  
Hiroyuki Tomita ◽  
...  
Keyword(s):  
Insertional Mutagenesis ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Malignant Cell ◽  
Precision Oncology ◽  
Oncogenic Viruses ◽  
Barr Virus ◽  
Human T Cell ◽  
Tumor Viruses ◽  
Tumor Virus

Cancer arises from the accumulation of genetic and epigenetic alterations. Even in the era of precision oncology, carcinogens contributing to neoplastic process are still an important focus of research. Comprehensive genomic analyses have revealed various combinations of base substitutions, referred to as the mutational signatures, in cancer. Each mutational signature is believed to arise from specific DNA damage and repair processes, including carcinogens. However, as a type of carcinogen, tumor viruses increase the cancer risk by alternative mechanisms, including insertional mutagenesis, viral oncogenes, and immunosuppression. In this review, we summarize virus-driven carcinogenesis to provide a framework for the control of malignant cell proliferation. We first provide a brief overview of oncogenic viruses and describe their implication in virus-related tumors. Next, we describe tumor viruses (HPV, Human papilloma virus; HBV, Hepatitis B virus; HCV, Hepatitis C virus; EBV, Epstein–Barr virus; Kaposi sarcoma herpesvirus; MCV, Merkel cell polyoma virus; HTLV-1, Human T-cell lymphotropic virus, type-1) and tumor virus-related cancers. Lastly, we introduce emerging tumor virus candidates, human cytomegalovirus (CMV), human herpesvirus-6 (HHV-6) and adeno-associated virus-2 (AAV-2). We expect this review to be a hub in a complex network of data for virus-associated carcinogenesis.

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