A Novel Class of Growth Factors Related to Herpesviruses

Konvalina, I.; Gašperík, Juraj; Golais, F

doi:10.2754/avb200271010029

Cited by 7 publications

(9 citation statements)

References 33 publications

(22 reference statements)

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“…5b) The fact that photoinactivated syncytial HSV-1 HSZP syn+ did not induce the morphological changes either in nontransformed NIH3T3 and MRC-5 cells or transformed A549 cells suggest that cells of all these cell lines infected with this virus did not produce compounds resembling growth factors, HRGF, previously shown in cells transformed by some herpesviruses. We found that photoinactivated HSZP is not capable of transforming non-transformed cells and suppressing the transformed phenotype of transformed cells, what is consistent with previous finding that syncytial strains of HSV-1 failed to produce HRGF (Golais et al, 1992a,b;Konvalina et al, 2002). However, this finding is very interesting and needs further studies.…”

Section: Resultssupporting

confidence: 92%

“…These putative HRGF have the ability to transform normal non-transformed cells and to suppress the transformed phenotype when added to transformed cells. Both activities of putative growth factors could be neutralized not only by antisera to the corresponding virus, but also by some monoclonal antibodies directed against viral gB glycoproteins (Golais et al, 1988(Golais et al, , 1992aKonvalina et al, 2002;Šupoliková et al, 2015). It has been also found that non-syncytial but not syncytial strains of HSV-1 were able to produce these compounds during infection of cells (Golais et al, 1992a,b).…”

Section: Introductionmentioning

confidence: 99%

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Herpes simplex viruses type 1 and 2 photoinactivated in the presence of methylene blue transform human and mouse cells in vitro

Michútová¹,

Mrázová²,

Kúdelová³

et al. 2017

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Three strains of herpes simplex virus, K17syn- and HSZPsyn+ of type 1 (HSV-1) and USsyn- of type 2 (HSV-2), were photoinactivated in the presence of methylene blue and used to infect 3 cell lines, normal human lung tissue cells (MRC-5), mouse epithelial cells (NIH3T3), and human lung carcinoma cells (A549). The virus titer and phenotype of cells were evaluated to compare the characteristics of normal and carcinoma cells infected with non-syncytial (non-syn) and syncytial (syn) strains of herpes simplex viruses. We found that the cells of both normal cell lines infected with photoinactivated K17syn- and USsyn- but not HSZPsyn+ acquired transformed phenotype accompanied by the presence of virus. Surprisingly, the infection with photoinactivated viruses K17syn- and USsyn- but not HSZPsyn+ resulted in the suppression of the transformed phenotype of A549 cells. Using nested PCR, herpesviral DNA was identified in newly transformed cells and cells that lost the transformed phenotype. The effect of putative herpesvirus-related growth factors (HRGF) produced by cells infected with photoinactivated viruses was quantified and compared. Since methylene blue is currently used in phototherapy of herpetic lesions, these results raise the question of whether such therapy is risky to human health.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Herpes simplex viruses type 1 and 2 photoinactivated in the presence of methylene blue transform human and mouse cells in vitro

Michútová¹,

Mrázová²,

Kúdelová³

et al. 2017

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“…It was previously postulated that HSGF and MHGF consist of several components [1,13]. Because the transforming activity of both HSGF and MHGF can be abolished by anti-gB antibodies, it was assumed that gB protein could be 1 component of HSGF as well as of MHGF [13,30].…”

Section: Figmentioning

confidence: 99%

“…Some herpesviruses and poxviruses have genes that encode secretory proteins with structural similarity to cellular growth factors [1]. The first growth factors related to herpesviruses were obtained from the alphaherpesviruses, pseudorabies virus (PRGF) and herpes simplex virus (HSV) type 1 and type 2 (HSGF-1 and HSGF-2) [2,3,4].…”

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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“…Podobný faktor bol dokázaný aj v bunkách transformovaných s MHV-68 [104]. Tieto rastové faktory asociované s herpetickými vírusmi boli zatiaľ dokázané len v podmienkach in vitro, ale predpokladá sa, že k ich produkcii by mohlo dochádzať aj v infikovanom organizme počas perzistentnej alebo latentnej infekcie [105]. Dôležitej-šia je však z tohto hľadiska ich schopnosť meniť transformované bunky na bunky s normálnym, netransformovaným fenotypom, ktoré by potenciálne mohli meniť aj fenotyp nádorových buniek v organizme.…”

Section: Experimentálne šTúdieunclassified

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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A Novel Class of Growth Factors Related to Herpesviruses

Abstract: Konvalina I.,

Cited by 7 publications

References 33 publications

Herpes simplex viruses type 1 and 2 photoinactivated in the presence of methylene blue transform human and mouse cells in vitro

Herpes simplex viruses type 1 and 2 photoinactivated in the presence of methylene blue transform human and mouse cells in vitro

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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