The prevalence of human cytomegalovirus DNA in gliomas of Brazilian patients

Fonseca, Renata; Kawamura, Marcia Tie; Oliveira, Jorge Henrique Caldeira de; Teixeira, Anselmo; Alves, Gilda; Carvalho, Maria da Glória da Costa

doi:10.1590/s0074-02762012000700020

Cited by 25 publications

(12 citation statements)

References 10 publications

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“…Clearly, sustained activation of PDGFRα signaling can drive early neoplastic changes in glioma development [11]and PDGFRα plays a major role in glioblastoma pathogenesis. Since HCMV gB protein expression has been detected in a majority of glioblastomas in vivo by several groups [2, 21, 22], and we show that gB functions essentially as an authentic PDGFR ligand, our data indicate that HCMV is exerting autocrine and paracrine oncogenic effects in vivo.…”

Section: Discussionsupporting

confidence: 63%

HCMV glycoprotein B is expressed in primary glioblastomas and enhances growth and invasiveness via PDGFR-alpha activation

et al. 2014

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Our laboratory first demonstrated that human cytomegalovirus (HCMV) is associated with the most deadly form of primary brain tumor, glioblastoma (GBM). We showed that HCMV glycoprotein B (gB) mediates viral cellular entry via the receptor tyrosine kinase PDGFR-alpha (PDGFRα), resulting in activation of the PI3K/Akt pathway, a critical signaling axis gliomagenesis. Here, we investigated the effects of gB overexpression on glioma progression. We demonstrate that gB is endogenously expressed in primary GBM samples and show that ectopic gB expression in glioma cells induced sustained phosphorylation of PDGFRα, Akt, and Src. Recombinant gB protein and the whole virus enhanced invasion of primary glioblastoma cells into Matrigel and rat brain slices, and this effect was specifically inhibited by neutralizing antibodies to either gB or PDGFRα. Importantly, neutralizing antibodies to gB significantly inhibited the invasiveness of patient-derived HCMV-positive glioblastoma cells, suggesting that functional inhibition of this viral protein could hinder glioblastoma progression. gB overexpression promoted in vivo glioma growth and enhanced phosphor-Akt levels and tumor cell dispersal relative to controls. Taken together, our results demonstrate that HCMV gB promotes key hallmarks of glioblastoma and suggest that targeting gB may have therapeutic benefits for patients with HCMV -positive gliomas.

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Section: Discussionsupporting

confidence: 63%

HCMV glycoprotein B is expressed in primary glioblastomas and enhances growth and invasiveness via PDGFR-alpha activation

et al. 2014

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“…Pneumonitis, hepatitis, nephritis, and gastroenteritis/colitis can occur following immune suppression [1,4,10,18,24,25]. HCMV has also been suggested to play a role in atherosclerosis and glioma progression [13,16,17,20,21,[26][27][28]. but, in these immunocompetent individuals, these reactivation events are also subclinical.…”

Section: Review Of the Literature And The Development Of Tissue Cultumentioning

confidence: 99%

Human Cytomegalovirus Latency: Targeting Differences in the Latently Infected Cell with a View to Clearing Latent Infection

Poole

Wills

Sinclair

2014

New Journal of Science

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Human cytomegalovirus (HCMV) is a human herpesvirus which causes little or no disease in the immunocompetent. However, in immunocompromised individuals, neonates, or patients on immune suppressive therapies, HCMV can cause significant morbidity and mortality in some patient groups. As with all herpesviruses, HCMV has two life cycle phases: a productive phase, where new virions are produced and a latent phase where there is a restricted gene transcription profile and no new virion production. Currently available antivirals target the productive phase of HCMV infection and, although these have greatly decreased the severity of HCMV-induced disease in immunocompromised or immunosuppressed individuals, they often have associated toxicities, routinely result in selection of drug resistant viral mutants, and, importantly, they do not target cells latently infected with virus. Thus, there is a real need to derive novel antiviral therapies which, not least, are also able to target latent infection. In this paper, we describe recent work which has begun to analyse changes in the cell associated with latent infection and the possibility that these latencyassociated changes in cell phenotype could be targeted by novel chemo-or immunotherapeutic strategies in order to diminish, or even clear, latent infection at least in some specific clinical settings.

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“…More recent studies have also confirmed the presence of the HCMV genome and viral proteins in a high percentage of glioblastoma multiforme. Mitchell et al [] (93% by IHC assay of IE1); Slinger et al [] (100% by IHC assay of IE and US28 antigens); Lucas et al [] (51% by IHC assay of pUL83); Soroceanu et al [] (65% by IHC assay of pUS28); Ranganathan et al [] (70% by PCR assay of multiple HCMV genome regions); Fonseca et al [] (36% by PCR assay of pUL83) Rahbar et al [] (99% by IHC against IE antigen) and Rahbar et al [] (99% by IHC assay of IE antigen). Nowadays the consensus is that HCMV is present in most, if not all glioblastoma multiforme tumors, and that it likely modulates the malignant phenotype of the tumor, being therefore considered an oncomodulatory agent [Dziurzynski et al, ].…”

Section: Introductionmentioning

confidence: 99%

High prevalence of HCMV and viral load in tumor tissues and peripheral blood of glioblastoma multiforme patients

Santos

Stangherlin

Figueiredo

et al. 2013

Journal of Medical Virology

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Glioblastoma multiforme is the most prevalent and malignant tumor of the central nervous system. In the last few years, accumulating evidence has suggested an association between human cytomegalovirus (HCMV) infection and glioblastoma multiforme. In this study, tumor tissues and peripheral blood of patients with glioblastoma multiforme were examined for the presence of HCMV DNA. Twenty-two fresh surgical brain specimens and 20 peripheral blood samples were analyzed by real-time PCR (qPCR) and hemi-nested PCR (nPCR) for the presence of pp65 and (glycoprotein B) gB viral genomic regions, respectively. HCMV DNA was detected in the majority of the tumor samples analyzed (95% by qPCR and 91% by nPCR). About half of the patients with tumors positive for HCMV also had detectable viral DNA in their peripheral blood (47% by qPCR and 61% by nPCR). Genome copy numbers were determined and in the majority of the tumor samples cellular DNA outnumbers viral DNA (average of 1 infected cell in 33 cells). The gB genotypes were determined in HCMV-positive samples and gB2 was the most prevalent genotype in the tumor and blood samples. The results show a high prevalence of HCMV in glioblastoma multiforme samples reinforcing a possible association between HCMV infection and tumor development.

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The prevalence of human cytomegalovirus DNA in gliomas of Brazilian patients

Abstract: Members of the

Cited by 25 publications

References 10 publications

HCMV glycoprotein B is expressed in primary glioblastomas and enhances growth and invasiveness via PDGFR-alpha activation

HCMV glycoprotein B is expressed in primary glioblastomas and enhances growth and invasiveness via PDGFR-alpha activation

Human Cytomegalovirus Latency: Targeting Differences in the Latently Infected Cell with a View to Clearing Latent Infection

High prevalence of HCMV and viral load in tumor tissues and peripheral blood of glioblastoma multiforme patients

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