The Human Cytomegalovirus, from Oncomodulation to Oncogenesis

Herbein, Georges

doi:10.3390/v10080408

Cited by 132 publications

(143 citation statements)

References 140 publications

(202 reference statements)

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“…22,23 Chronic viral infection of mice with murine cytomegalovirus (CMV) increased epithelial turnover and wound repair via antiviral cytokine type I interferons (IFNs), 24 but CMV infection can promote cancer malignancy; this phenomenon is known as 'oncomodulation'. 25,26 Recent metagenomic studies have revealed that virus infection sometimes confers benefits including the regulation of microbiota in the gut. Bacteriophages are abundant in the gut and are thought to modulate the gut microbiota by infecting specific bacterial populations.…”

Section: Beneficial Effects Of Viral Infection On Mammalian Hostsmentioning

confidence: 99%

Villains or heroes? The raison d'être of viruses

Watanabe

Kawaoka

2020

Clin & Trans Imm

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The relationship between humans and viruses has a long history. Since the first identification of viruses in the 19th century, we have considered them to be 'pathogens' and have studied their mechanisms of replication and pathogenicity to combat the diseases that they cause. However, the relationships between hosts and viruses are various and virus infections do not necessarily cause diseases in their hosts. Rather, recent studies have shown that viral infections sometimes have beneficial effects on the biological functions and/or evolution of hosts. Here, we provide some insight into the positive side of viruses.

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Section: Beneficial Effects Of Viral Infection On Mammalian Hostsmentioning

confidence: 99%

Villains or heroes? The raison d'être of viruses

Watanabe

Kawaoka

2020

Clin & Trans Imm

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“…Some clinical studies have suggested a role for CMV in the pathogenesis of glioblastoma, an aggressive neoplasm of the central nervous system [62,63] but subsequent studies have shown conflicting results concerning HCMV identification in tumours [64][65][66][67][68], a fundamental requisite according to the criteria proposed by Frederick and Relman for the identification of diseases caused by viruses [69,70]. Therefore, a consensus to consider CMV as an oncogenic virus or merely an oncomodulatory virus that may cause tumour cells to become more aggressive has not been reached [71]. On the other hand, CMV infection may have anti-tumour effects related to an increased antitumoral immune response [72].…”

Section: Mouse-adapted Zebov Ip Challengementioning

confidence: 99%

“…Advantages of using a full-length protein include the elicitation of broad immune responses in various MHC backgrounds which increases the prospect of a protective response toward critical epitopes in genetically heterogeneous populations [149]. A comparison of MCMV-based vectors encoding either the full length gene of the prostate-specific antigen (PSA) (MCMV/PSA FL ) or a PSA-derived epitope (MCMV/PSA [65][66][67][68][69][70][71][72][73] ) within the ie2 gene [150] showed that only MCMV/PSA [65][66][67][68][69][70][71][72][73] protected against tumour challenge with a PSA-expressing adenocarcinoma, although both vectors induced an inflationary response of PSA-specific CD8 T cells. As MCMV/PSA FL induced poor CD8 response upon challenge, the mechanism of CD8 suppression was suspected to depend on differences in the functionality of responding cells.…”

Section: Cellular Response-t Cellsmentioning

confidence: 99%

Vaccine Vectors Harnessing the Power of Cytomegaloviruses

2019

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Cytomegalovirus (CMV) species have been gaining attention as experimental vaccine vectors inducing cellular immune responses of unparalleled strength and protection. This review outline the strengths and the restrictions of CMV-based vectors, in light of the known aspects of CMV infection, pathogenicity and immunity. We discuss aspects to be considered when optimizing CMV based vaccines, including the innate immune response, the adaptive humoral immunity and the T-cell responses. We also discuss the antigenic epitopes presented by unconventional major histocompatibility complex (MHC) molecules in some CMV delivery systems and considerations about routes for delivery for the induction of systemic or mucosal immune responses. With the first clinical trials initiating, CMV-based vaccine vectors are entering a mature phase of development. This impetus needs to be maintained by scientific advances that feed the progress of this technological platform.Vaccines 2019, 7, 152 2 of 28 CMV-based vaccines, the large pool of functional antigen-specific T cells in the periphery and the possibility to modify CMV genomes due to improvements in viral genetics [11] draw a strong interest to CMV as a vaccine vector [12,13] (Table 1). The inflationary response appears linked to immune protection [14,15] and has been proposed as a target for immunization induction [16]. Vaccines 2019, 7, 152 3 of 28 Full-length HPV16 E6 and E7 Antigen fused to the C-terminus of ie2 Transient limitation of tumour cell growth MCMV IE2E7 [14] MHC-I restricted HPV16 E7 49-57 epitope Epitope fused to the C-terminus of ie2 No tumour cell growth upon challenge MCMV-M79-FKBP-E7 [36] MCMV Smith Strain with FKBP-mediated destabilization of the essential M79 gene Vaccines 2019, 7, 152 5 of 28Besides the exceptional induction of adaptive immune response in humans [2,37], CMV possesses assets that conveniently address weaknesses common to other vector candidates. The cloning of CMV genomes as bacterial artificial chromosomes in Escherichia coli [38] has allowed genetic engineering approaches to effectively express multiple exogenous immunogens or modify large genome portions [39,40]. Furthermore, CMV is known to superinfect hosts with a history of prior exposure to the virus [41] due to its immune evasive properties that protect the virus from recognition by primed T-cells [42] and CMV vectors induce protective immunity in experimentally vaccinated animals with documented prior exposure to 36]. Therefore, CMV vector candidates would avoid immune interference as described for AdV. CMV is a pathogenic organism in immunodeficient populations [43] or in congenitally infected children. Therefore, it is imperative for any HCMV vaccine vector to be attenuated. The generation of replication deficient CMVs that maintain their immunogenicity [36,44] and the modification of genome portions that contain evasions genes [45], as well as the insertion of activating ligands to increase immune control of CMV [46][47][48] are strategies that will be described in this review. Inter...

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“…Ép immunrendszerű egyénekben is észleltek súlyos gyomorbél rendszeri (gastritis, ileitis, colitis), idegrendszeri (meningoencephalitis, myelitis, radiculopathia), hematológiai (haemolyticus anaemia, pancytopenia, disszeminált intravascularis coagulatio), vascularis (thromboembolia), szemészeti (chorioretinitis, uveitis, papillitis), illetve pulmonalis (pneumonitis) komplikációkat [6]. Lehetséges, hogy a vírus elősegíti malignus daganatok propagációját vagy akár azok kialakulását [7]. A hCMV-szeropozitivitás kedvezőtlenül befolyásolta a várható túlélést, még akkor is, ha a halálozás egyéb kockázati tényezőinek hatását statisztikai módszerekkel kiegyenlítették (HR, 1,16 [95% CI, 1,07-1,26]) [8].…”

Section: Humán Cytomegalovirusfertőzés éP Immunrendszerű Személyekbenunclassified

Aktualitások a sérült immunitású betegek cytomegalovirusinfekcióinak ellátásában. I. Epidemiológia és klinikai szempontok

Sinkó

2019

Orvosi Hetilap

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Human cytomegalovirus is a DNA virus with a global prevalence of 40–100%. In humans, primary infection is followed by a lifelong latent persistent phase. Even in individuals developing adequate specific immunity, interactions with the resident virus do probably occur. Clinically significant problems, however, appear primarily in immunocompromised hosts. As a result of an impaired T-cell mediated immunity, viral reactivation as well as a viral disease resulting in organ damage can develop. Most severely affected are HIV positive persons in AIDS stage and individuals undergoing solid organ or stem cell transplantation. As vital functions and survival may adversely be affected by cytomegalovirus reactivation and disease, it is of paramount significance to evaluate evident risk factors. Viral reactivation and organ specific disease can be detected by several methods based on conventional and molecular biological and histological diagnostic techniques. An up-to-date management of affected patient groups requires a meticulous assessment of the possible risk for cytomegalovirus infection and development of an adequate antiviral strategy. Orv Hetil. 2019; 160(3): 83–92.

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The Human Cytomegalovirus, from Oncomodulation to Oncogenesis

Cited by 132 publications

References 140 publications

Villains or heroes? The raison d'être of viruses

Villains or heroes? The raison d'être of viruses

Vaccine Vectors Harnessing the Power of Cytomegaloviruses

Aktualitások a sérült immunitású betegek cytomegalovirusinfekcióinak ellátásában. I. Epidemiológia és klinikai szempontok

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