Cytomegalovirus and Epstein-Barr Virus in Breast Cancer

Richardson, Ann; Currie, Margaret J.; Robinson, Bridget A.; Morrin, Helen; Phung, Yen; Pearson, John; Anderson, Trevor P.; Potter, John D.; Walker, Logan C.

doi:10.1371/journal.pone.0118989

Cited by 88 publications

(71 citation statements)

References 61 publications

(110 reference statements)

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“…We further showed evidence that replication of the HK2 genome occurred in viral particles as well as in the infected cell (53), resembling the viral replication mechanism of spumaviruses (52). The infectious material of HK2 viruses can circularize and create episomal forms (51), similar to transforming viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) (58,59). It is possible, then, that despite no proof of HK2 integration, replication and episomal formation of HK2 viruses could lead to carcinogenesis or other disturbances in cellular replication in human cells.…”

Section: Discussionmentioning

confidence: 84%

Susceptibility of Human Endogenous Retrovirus Type K to Reverse Transcriptase Inhibitors

Contreras-Galindo

Dube

Fujinaga

et al. 2017

J Virol

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Human endogenous retroviruses (HERVs) make up 8% of the human genome. The HERV type K (HERV-K) HML-2 (HK2) family contains proviruses that are the most recent entrants into the human germ line and are transcriptionally active. In HIV-1 infection and cancer, HK2 genes produce retroviral particles that appear to be infectious, yet the replication capacity of these viruses and potential pathogenicity has been difficult to ascertain. In this report, we screened the efficacy of commercially available reverse transcriptase inhibitors (RTIs) at inhibiting the enzymatic activity of HK2 RT and HK2 genomic replication. Interestingly, only one provirus, K103, was found to encode a functional RT among those examined. Several nucleoside analogue RTIs (NRTIs) blocked K103 RT activity and consistently inhibited the replication of HK2 genomes. The NRTIs zidovudine (AZT), stavudine (d4T), didanosine (ddI), and lamivudine (3TC), and the nucleotide RTI inhibitor tenofovir (TDF), show efficacy in blocking K103 RT. HIV-1-specific nonnucleoside RTIs (NNRTIs), protease inhibitors (PIs), and integrase inhibitors (IIs) did not affect HK2, except for the NNRTI etravirine (ETV). The inhibition of HK2 infectivity by NRTIs appears to take place at either the reverse transcription step of the viral genome prior to HK2 viral particle formation and/or in the infected cells. Inhibition of HK2 by these drugs will be useful in suppressing HK2 infectivity if these viruses prove to be pathogenic in cancer, neurological disorders, or other diseases associated with HK2. The present studies also elucidate a key aspect of the life cycle of HK2, specifically addressing how they do, and/or did, replicate. Endogenous retroviruses are relics of ancestral virus infections in the human genome. The most recent of these infections was caused by HK2. While HK2 often remains silent in the genome, this group of viruses is activated in HIV-1-infected and cancer cells. Recent evidence suggests that these viruses are infectious, and the potential exists for HK2 to contribute to disease. We show that HK2, and specifically the enzyme that mediates virus replication, can be inhibited by a panel of drugs that are commercially available. We show that several drugs block HK2 with different efficacies. The inhibition of HK2 replication by antiretroviral drugs appears to occur in the virus itself as well as after infection of cells. Therefore, these drugs might prove to be an effective treatment by suppressing HK2 infectivity in diseases where these viruses have been implicated, such as cancer and neurological syndromes.

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Section: Discussionmentioning

confidence: 84%

Susceptibility of Human Endogenous Retrovirus Type K to Reverse Transcriptase Inhibitors

Contreras-Galindo

Dube

Fujinaga

et al. 2017

J Virol

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“…2016; 11(3):e34806. (11,18,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). Table 1 shows a summary of the EBV-DNA positive subjects according to nationality, types of sample, and kinds of control tissue in the 20 selected studies.…”

Section: Resultsmentioning

confidence: 99%

Epstein-Barr Virus Infection and Risk of Breast Cancer: An Adaptive Meta-Analysis for Case-Control Studies

Bae

Kim

2016

Arch Clin Infect Dis

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Context: The association between 'Epstein-Barr' virus (EBV) and breast cancer risk still remains controversial. A Systemic Review (SR) published in 2012 reported that there might be a statistically significant association between EBV and risk of breast cancer. However, errors were found in the appraisal process of the concerned SR. Objectives:The aim of this report was to conduct an adaptive meta-analysis with additional extraction of relevant papers published up until September 2015.Data Sources: The lists of references, cited articles and related articles provided by PubMed were made using the articles selected in the previous SR.Study Selection: Among these articles, only case-control studies using Polymerase Chain Reaction (PCR) techniques to detect EBV DNA in tissues were selected. Data Extraction: The summary odds ratio (SOR) and the 95% confidence interval (CI) were calculated though meta-analysis.Results: A total of 20 case-control studies were selected, and the total numbers of subjects in the case and control groups were 1947 and 1010, respectively. The findings of this meta-analysis revealed that EBV infection might increase the risk of breast cancer (SOR = 3.84, 95% CI: 2.24-6.58; I-squared = 62.2%). Sub-group analyses by region, sample type, and control tissue showed that a statistical significance of the risk was still secured. Conclusions:The findings of the meta-epidemiological study support that EBV infection may increase the risk of breast cancer. Nested case-control studies are required in the future.

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“…Currently, increasing evidence has highlighted the relationship between HCMV infection and human cancers. HCMV genomes or gene products have been detected in several cancers including malignant glioma, cervical carcinoma, Kaposi's sarcoma and breast cancer [3–6]. In vitro studies have verified the capacity of HCMV for transforming cells and increasing tumourigenicity [7].…”

Section: Introductionmentioning

confidence: 99%

Human cytomegalovirus infection and colorectal cancer risk: a meta-analysis

et al. 2016

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Human cytomegalovirus infection (HCMV) has been recently considered as a factor for tumorigenesis. The current study used meta-analytical techniques to explore the prevalence of HCMV in tumor tissues and the relationship between human cytomegalovirus and colorectal cancer (CRC) risk. 11 studies detecting HCMV DNA in tumor tissues were included in meta-analysis. The prevalence rate and odds ratio (OR) were two main parameters. The overall prevalence of human cytomegalovirus DNA in tumor tissues were 27.5% (95% CI = 17.2%−37.8%). Binary logistic regression showed that the studies reported before 2010 involving formalin-fixed specimens from patients in developed region represented a lower proportion of HCMV. The tumor tissues had a significantly higher rate of virus infection compared with normal tissues (OR = 6.59, 95% CI = 4.48−9.69, I2 = 0%, P = 0.71). Subgroup analysis revealed the prevalence of the virus didn't differ in patients with different tumor stages, in tumor cells with different histologic grades, also in different kinds of specimen (polyp and adenocarcinoma). The results of current study suggested a statistically association between the virus infection and an increased risk of colorectal cancer.

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Cytomegalovirus and Epstein-Barr Virus in Breast Cancer

Cited by 88 publications

References 61 publications

Susceptibility of Human Endogenous Retrovirus Type K to Reverse Transcriptase Inhibitors

Susceptibility of Human Endogenous Retrovirus Type K to Reverse Transcriptase Inhibitors

Epstein-Barr Virus Infection and Risk of Breast Cancer: An Adaptive Meta-Analysis for Case-Control Studies

Human cytomegalovirus infection and colorectal cancer risk: a meta-analysis

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