Murine Gammaherpesvirus (MHV-68) Transforms Cultured Cells in vitro

Mrázová, Veronika; Betáková, Tatiana; Kúdelová, M; Šupolíková, Miroslava; Lachová, Veronika; Lapuníková, B.; Golais, F

doi:10.1159/000370071

Cited by 11 publications

(17 citation statements)

References 16 publications

(14 reference statements)

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“…However, it was demonstrated in some cases that NR was not effective in the treatment of herpetic lesions [14][15][16] . In our previous study, we demonstrated that UV-inactivated MHV-68 can transform cells in vitro [27] , thus resembling the transforming ability of several UV-inactivated herpesviruses belonging to the subfamily Alphaherpesvirinae, such as HSV1, HSV2, and EHV [24][25][26]39] . Recent studies have reported that normal cell lines such as MRC-5 and NIH-3T3 (used in this study) cultured in the presence of MB acquired a transformed phenotype accompanied by the presence of virus when they were infected with photoinactivated nonsyn strains (K17 and Kupka) but not syn strains (HSZP) of HSV-1 [40] .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, transformation of MRC-5 and NIH-3T3 cells in vitro was demonstrated after infection with UV-irradiated alpha-herpesviruses, HSV-1 and HSV-2 [24][25][26] . Moreover, UV-irradiated murine gamma-herpesvirus 68 (MHV-68) enabled the transformation of human and mouse dermal fibroblast cells in which the disappearance of actin bundles was demonstrated [27] .…”

Section: Introductionmentioning

confidence: 99%

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Transformation of Cells by Photoinactivated Murine Gamma-Herpesvirus 68 during Nonproductive and Quiescent Infection

et al. 2017

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Infection of human MRC-5 cells and mouse NIH-3T3 cells with a murine gamma-herpesvirus (MuHV-4 strain 68; MHV-68) photoinactivated by visible light in the presence of methylene blue (MB) resulted in nonproductive infection and the appearance of morphologically transformed cells. Two stably transformed cell lines were derived from both of these cell types and were confirmed to contain both viral DNA and antigen. Next, a quiescent MHV-68 infection in MRC-5 and NIH-3T3 cells was established after cultivation at 41°C in the presence of phosphonoacetic acid. Following the exposure of quiescently infected cells to visible light for 120 s (5 times daily for 6 days) in the presence of MB, both MRC-5 and NIH-3T3 cells were observed to acquire transformed phenotypes. The cytopathic effect was observed in cells after 4-5 passages, after which the cells degenerated. However, when human interferon (IFN)-α and mouse IFN-β were added to the media of quiescently infected MRC-5 and NIH-3T3 cells during the photoinactivating procedure, 2 stable transformed cell lines containing both viral DNA and the antigen were obtained and resembled those attained following nonproductive infection with photoinactivated virus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transformation of Cells by Photoinactivated Murine Gamma-Herpesvirus 68 during Nonproductive and Quiescent Infection

et al. 2017

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“…PRGF and HSGF-2 exhibit transformation activity in vitro [2,8,9,10,11]. Recently, similar activities of murine gammaherpesvirus (MHV-68) were described [12,13]. …”

Section: Figmentioning

confidence: 99%

“…The oncogenic potential of some alpha- or betaherpesviruses has been studied for over 2 decades. The transforming activity of MHV-68 was demonstrated on the tumor cell line S11 derived from MHV-68 infected mice growing into tumors in nude mice, human dermal fibroblasts, and mouse NIH/3T3 cells infected with ultraviolet-irradiated MHV-68 [12,31]. Further studies will be required to determine differences in the composition of MHGFA and MHGFW and the possible role of gB, US3, UL24, and other viral and cellular proteins in cell transformation and oncogenesis.…”

Section: Figmentioning

confidence: 99%

Transforming Activity of Murine Herpesvirus 68 Putative Growth Factor Is Related to the Ability to Change Cytoskeletal Structure

Lachová

Svetlíková²,

Golais³

et al. 2016

Intervirology

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Murine herpesvirus 68 (MHV-68) can transform cells in vitro and in vivo. We investigated putative murine herpesvirus growth factors (MHGFs) obtained by the separation of cell-free media from MHV-68-transformed cells on an FPLC Sephadex G15 column. The transforming activity of the MHGFA fraction was related to depolymerization of actin, disruption of the microtubule network, and punctate-reticular changes of the Golgi. The MHGFW fraction had only repressing activity on the transformed phenotype. Incubation of MRC-5 cells with MHGFW resulted in reticular changes of the Golgi apparatus, minor depolymerization of actin filaments, and no detectable changes of the microtubule network. Reorganization of the actin cytoskeleton is associated with oncogenesis. Further study of the MHGFs from herpesviruses and proteins responsible for changes in the organization of the cytoskeleton could give insight into the cell transformation mechanism and oncogenesis.

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“…V bunkách transformovaných s MHV-68 bola dokázaná víru-sová DNA metódou PCR a vírusový antigén pomocou imunofluorescencie. Imunofluorescenčné štúdie však navyše ukázali, že v transformovaných bunkách dochádza k rozpadu aktínových filamentov [52]. Podobne bola možná transformácia po infekcii fotoinaktivovaným vírusom, t. j. ak bol vírus zafarbený neutrálnou červeňou alebo metylénovou modrou a ožiarený viditeľným svetlom [53][54][55].…”

Section: Mechanizmus "Hit and Run"unclassified

A Possible Role of Human Herpes Viruses Belonging to the Subfamily Alphaherpesvirinae in the Development of Some Cancers

Mrázová¹,

Golais²,

Búda³

2018

Klin Onkol

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SúhrnĽudské vírusy herpes simplex typ 1 a 2 (HSV-1, HSV-2) sa väčšinou na základe séroepidemiologických štúdií dávajú do súvislosti s viacerými nádorovými ochoreniami. Nepredpokladá sa však, že by pri vzniku nádorov mali priamu úlohu. Pôsobia pravdepodobne len ako kofaktory. Experimentálne sa podarilo dokázať ich schopnosť transformovať bunky in vitro odstránením ich vysokej lytickej schopnosti určitou dávkou UV žiarenia alebo fotoinaktiváciou v prítomnosti fotosenzitizérov, napr. neutrálnej červene alebo metylénovej modrej alebo kultiváciou v podmienkách potláčajúcich ich lytickú schopnosť. K vzniku nádorov by mohli prispieť niekoľkými mechanizmami. Podľa mechanizmu "hit and run" navodí vírusová DNA interakciou s bunkovou DNA a indukciou genetických a epigenetických zmien len iniciáciu transformácie a na ďalšom procese neoplastickej progresie sa už nepodiela. Podľa mechanizmu "hijacking" môže vírusový produkt v infikovaných bunkách aktivovať signálnu dráhu a spôsobiť tým nekontrolovateľnú proliferáciu. Takýmto produktom je napr. produkt génu HSV-2 označovaného ako ICP10, ktorý kóduje onkoproteín RR1PK aktivujúci signálnu dráhu Ras. V dvoch prípadoch, v prípade serózneho karcinómu vaječníkov a v niektorých nádoroch prostaty boli dokázané vírusom kódované mikroRNA ako možní spolopôvodcovia vzniku nádorov. Možnú úlohu by mohli hrať aj nedávno popísané rastové faktory asociované s herpetickými vírusmi s transformačným a transformáciu potláčajúcim účinkom. Nakoniec, existuje rad dôkazov, že HSV-2 môže zvyšovať riziko vzniku cervikálneho karcinómu po infekcii s ľudskými papilómovými vírusmi. Kľúčové slová HSV-1 -HSV-2 -nádory -mechanizmy transformácie SummarySeroepidemiological studies suggest that human herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) are linked with several types of cancer; however, they do not appear to play a direct role and are considered to be cofactors. The abilities of HSV-1 and -2 to transform cells in vitro can be demonstrated by suppress ing their lytic ability via irradiation with a specific dose of ultraviolet light, photoinactivation in the presence of photosensitizers (e. g., neutral red or methylene blue), and culture under specific conditions. Several mechanisms have been proposed to explain the actions of these viruses. Accord ing to the hit-and-run mechanism, viral DNA initiates transformation by interact ing with cellular DNA and thereby induc ing mutations and epigenetic changes, but is not involved in other stages of neoplastic progression. By contrast, accord ing to the hijack ing mechanism, viral products in infected cells can activate signal ing pathways and thereby cause uncontrolled proliferation. Such products include RR1PK, an oncoprotein that activates the Ras pathway and is encoded by the HSV-2 gene ICP10 . Virus-encoded microRNAs may act as cofactors in tumorigenesis of serous ovarian carcinoma and some prostate tumors. Herpes virus-associated growth factors that facilitate or suppress transformation may play important roles in tumor formation. Finally, there is much ...

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Murine Gammaherpesvirus (MHV-68) Transforms Cultured Cells in vitro

Cited by 11 publications

References 16 publications

Transformation of Cells by Photoinactivated Murine Gamma-Herpesvirus 68 during Nonproductive and Quiescent Infection

Transformation of Cells by Photoinactivated Murine Gamma-Herpesvirus 68 during Nonproductive and Quiescent Infection

Transforming Activity of Murine Herpesvirus 68 Putative Growth Factor Is Related to the Ability to Change Cytoskeletal Structure

A Possible Role of Human Herpes Viruses Belonging to the Subfamily Alphaherpesvirinae in the Development of Some Cancers

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