Characterization of Transcription Factor Binding to Human Papillomavirus Type 16 DNA during Cellular Differentiation

Carson, Andrew R.; Khan, Saleem A.

doi:10.1128/jvi.80.9.4356-4362.2006

Cited by 30 publications

(27 citation statements)

References 35 publications

(39 reference statements)

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“…These differences were statistically significant (P ≤ 0.00001). Similar observations were observed in other studies that also showed a decreasing trend of HPV with age [12][13][14][15]. This may be due to the role of acquired immunity, which probably clears the virus in older women; however, this needs further in-depth study.…”

Section: Discussionsupporting

confidence: 88%

Oncogenic human papilloma virus and cervical pre-cancerous lesions in brothel-based sex workers in India

Sarkar

Bhattacharya²,

Bhattacharyya

et al. 2008

Journal of Infection and Public Health

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A community-based cross-sectional study was conducted in brothel-based sex workers of West Bengal, Eastern India, to determine their oncogenic human papillomavirus (HPV) status and the presence of pre-cancerous lesions. A total of 229 sex workers from three districts of West Bengal participated in the study. All the study participants were interviewed with the aid of a pre-tested questionnaire to determine their sociodemographics, risk behaviour and risk perceptions after obtaining informed verbal consent. The interview was followed by collection of cervical cells from all participants using a disposable vaginal speculum and cervical cytobrush. Oncogenic HPV DNA was detected by real-time polymerase chain reaction (PCR). A simultaneous Papanicolaou test ('Pap smear') was performed to detect cervical cytological abnormalities. Overall, the prevalence of oncogenic HPV was found to be 25% (58/229) among the studied population. A subset (n=112) of the sample was tested separately to determine the existence and magnitude of HPV genotypes 16 and 18. The results showed that genotype 16 was prevalent in 10% (11/112), genotype 18 in 7% (8/112) and both genotype 16 and 18 in 7% (8/112). The HPV prevalence rate showed a decreasing trend with age, being 71.4% in the 10-19 years age group, 32.3% in the 20-29 years age group, 18.3% in the 30-39 years age group and 2.5% in the >or=40 years age group (statistically significant differences, P1 year, respectively. This difference was found to be statistically significant both by univariate and multivariate analysis. In this study, it was observed that sex workers with an average number of daily clients of six or more had an HPV prevalence of 67% (n=6), those with four to five clients had a prevalence of 45% (n=9), those with two to three clients had a prevalence of 30% (n=34) and those with one or less clients had a prevalence of 10% (n=9) (statistically significant differences, P=0.00003). Multivariate analysis showed a statistical association only with a duration of sex work of or=101 (OR=2.5; 95% CI 1.3-5). Regarding pre-cancerous lesions, 2 of 229 sex workers showed the presence of a low-grade squamous intraepithelial lesion along with high-risk HPV. Thus, 1% of the studied population suffer from a pre-cancerous lesion caused by high-risk HPV. This study concludes that young sex workers are particularly vulnerable to high-risk HPV, similar to human immunodeficiency virus (HIV). The observation of older sex workers relatively free from HPV supports the view of acquired immunity against HPV, which needs to be studied in-depth further. There is a need for a suitable community-based intervention programme targeted towards sex workers, with special reference to younger sex workers, for control and preve...

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Section: Discussionsupporting

confidence: 88%

Oncogenic human papilloma virus and cervical pre-cancerous lesions in brothel-based sex workers in India

Sarkar

Bhattacharya²,

Bhattacharyya

et al. 2008

Journal of Infection and Public Health

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“…To ensure that the reduction in viral genome amplification observed in the presence of caspase inhibitors was not attributable to inhibition of differentiation, we examined the expression of cytokeratin 10 (K10), which is a marker of differentiation and is expressed concurrently with genome amplification (24). Expression of K10 increased upon calcium-induced differentiation of CIN612 cells and was not diminished by treatment with Z-VAD-FMK (Fig.…”

Section: Hpv-mediated Caspase Activation Is Necessary For Viral Genomementioning

confidence: 99%

Human papillomaviruses activate caspases upon epithelial differentiation to induce viral genome amplification

Moody

Fradet-Turcotte

Archambault

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

103

121

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The life cycle of human papillomaviruses (HPVs) is linked to epithelial differentiation, with late viral events restricted to the uppermost stratified layers. Our studies indicated that HPV activates capases-3, -7, and -9 upon differentiation, whereas minimal activation was observed in differentiating normal keratinocytes. Activation occurred in the absence of significant levels of apoptosis, suggesting a potential role for caspases in the viral life cycle. In support of this, the addition of caspase inhibitors significantly impaired differentiation-dependent viral genome amplification. A conserved caspase cleavage motif was identified in the replication protein E1 ( 46 DxxD 49 ) that was targeted in vitro by both recombinant caspase-3 and caspase-7. Mutation of this site inhibited amplification of viral genomes, indicating that caspase cleavage is necessary for the productive viral life cycle. Our study demonstrates that HPV activates caspases upon differentiation to facilitate productive viral replication and represents a way by which HPV controls viral gene function in differentiating cells.replication ͉ pathogenesis ͉ apoptosis

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“…It is established that viral genomic DNA is packaged into chromatin utilizing cellular histones, which form specifically positioned nucleosomes [17,18] and that chromatin structure is rearranged upon differentiation favouring activation of late gene expression [19]. Several studies have documented dynamic differentiation-dependent changes in transcription factor binding to both the LCR and late promoter [20,21]. The binding pattern of a number of transcription factors including c-Myb, Pax5, NFATx (a nuclear factor of activated Tcells family member), C/EBPβ (CCAAT/enhancer-binding protein β) and YY1 (Yin and Yang 1) was changed upon keratinocyte differentiation and it is likely that combinations of these factors act to regulate late gene expression.…”

Section: Regulation Of Transcriptionmentioning

confidence: 99%

Human papillomavirus gene expression is controlled by host cell splicing factors

Klymenko

Graham

2012

Biochemical Society Transactions

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HPVs (human papillomaviruses) infect stratified epithelia and cause a variety of lesions ranging from benign warts to invasive tumours. The virus life cycle is tightly linked to differentiation of the keratinocyte it infects: papillomaviruses modulate host gene expression to ensure efficient virus replication. For example, the viral transcription factor E2 can directly up-regulate, in an epithelial differentiation-dependent manner, cellular SRSFs [SR (serine/arginine-rich) splicing factors] that control constitutive and alternative splicing. Changes in alternative splicing and the mechanisms controlling this for viral mRNAs have been the subject of intense exploration. However, to date experiments have only been carried out in model systems because the genetic systems suitable for studying alternative splicing of viral RNAs in the context of the virus life cycle are relatively recent and technically challenging. Now using these life cycle-supporting systems, our laboratory has identified SR proteins as important players in differentiation-dependent regulation of HPV gene expression. Better understanding of the role of cellular factors in regulating the virus life cycle is needed as it may help development of novel diagnostic approaches and antiviral therapies in the future.

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Characterization of Transcription Factor Binding to Human Papillomavirus Type 16 DNA during Cellular Differentiation

Cited by 30 publications

References 35 publications

Oncogenic human papilloma virus and cervical pre-cancerous lesions in brothel-based sex workers in India

Oncogenic human papilloma virus and cervical pre-cancerous lesions in brothel-based sex workers in India

Human papillomaviruses activate caspases upon epithelial differentiation to induce viral genome amplification

Human papillomavirus gene expression is controlled by host cell splicing factors

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