Genetic variations in the DNA replication origins of human papillomavirus family correlate with their oncogenic potential

Yılmaz, Gülden; Biswas-Fiss, Esther E.; Biswas, Subhasis B.

doi:10.1016/j.bbagen.2017.12.010

Cited by 8 publications

(18 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human papillomavirus (HPV) is a small, double-stranded DNA virus that replicates within skin and mucosal epithelial cells, and HPV is mainly transmitted via sexual contact. 1 , 2 The International Human Papillomavirus Reference Center recognises 227 HPV subtypes of 52 species [ www.hpvcenter.se , accessed on 2020-03-05]. The two most common low-risk (lr)HPV subtypes are HPV6 and HPV11, which cause genital warts and intraepithelial neoplasia.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Genotype Distribution of Human Papillomavirus Among Attendees at a Sexually Transmitted Diseases Clinic in Urban Tianjin, China

Xiang¹,

Han²,

Yu³

et al. 2021

IJGM

View full text Add to dashboard Cite

Background: Human papillomavirus (HPV) is linked to various cancers in males and females. The prevalence and genotype distribution of HPV vary depending on geographical region and the immunity provided by vaccines. Investigation of HPV epidemiology is of great meaning for the development of prevention programs. Methods: From January 2017 to September 2019, using PCR-reverse dot blot hybridisation, we determined the HPV subtypes in 2801 patients 17-89 years old at the sexually transmitted diseases (STD) clinic of Tianjin Medical University General Hospital. Results: The HPV infection rate was 50.79% in males and 50.64% in females. The most common HPV genotype in males and females was HPV6 (30.15% and 30.43%), followed by HPV16 (18.76% and 20.65%) and HPV11 (14.61% and 15.67%). Infection with a single HPV subtype predominated in both males and females, and the rate in males was higher than in females. By contrast, the rate of high-risk HPV (hrHPV) and low-risk HPV (lrHPV) mixed infection in females was higher than in males. Most HPV-positive patients were 20-39 years of age. The prevalence of infection with only hrHPV differed among the age groups; the peak age was 50 to 59 years. Conclusion:The HPV prevalence was higher among the STD clinic outpatients than the general population. Therefore, a large-scale survey of high-risk populations is needed. It is anticipated that HPV vaccines, regular education and physical examinations may have a significant impact on the prevention of HPV-related diseases in high-risk groups.

show abstract

Section: Introductionmentioning

confidence: 99%

Prevalence and Genotype Distribution of Human Papillomavirus Among Attendees at a Sexually Transmitted Diseases Clinic in Urban Tianjin, China

Xiang¹,

Han²,

Yu³

et al. 2021

IJGM

View full text Add to dashboard Cite

show abstract

“…One study has found that variation in the E2 binding sites of HPV 16 and HPV 18 cause differences in their affinities, which may lead to a change in the replication process and the modulation of carcinogenicity. However, the specific difference in carcinogenicity modulation between these two types is not yet clear and further investigation is required [27].…”

Section: Discussionmentioning

confidence: 99%

Human papillomavirus type 16 and 18 viral loads as predictors associated with abnormal cervical cytology among women in Saudi Arabia

Obeid

Almatrrouk

Khayat

et al. 2020

Heliyon

View full text Add to dashboard Cite

The detection of HPV viral DNA is regularly conducted with cervical screening. However, using a molecular marker such as the viral load may serve as a predictor associated with disease detection and progression. The present study aimed to screen for and genotype HPV among women in Saudi Arabia, develop and validate sensitive quantitative polymerase chain reaction (qPCR) assays to detect viral load for the two most common HPV types, namely 16 and 18, and assess whether HPV viral load could be used as a marker for cervical abnormality and disease progression. This study examined 733 specimens (both formalin-fixed paraffin embedded specimens and PAP smear samples) from women who underwent cervical screening. The specimens and samples were processed for DNA extraction and then tested for HPV DNA using nested PCR. Approximately 165 specimens (18%) were positive for HPV. Those specimens were genotyped using a reverse line blotting hybridization assay. The results indicated that the most common HPV types detected were a single infection with HPV 16 (51%) or with HPV 18 (28%) followed by infections with multiple HPV types (~7%). A qPCR TaqMan assay developed and validated in-house was used to determine viral load for HPV genotypes 16 (n ¼ 80) and 18 (n ¼ 45). Viral loads for both HPV types were significantly associated with cervical cytology grade (P < 0.05). The odds ratio (OR) for the HPV 16 viral load was high for specimens with cervical cancer (OR, 18.8; 95% CI, 4.3-82.9) or for those with high-grade squamous intraepithelial lesions (OR, 14.7; 95% Cl,). For the HPV 18 viral load, the OR was significant only for specimens with cervical cancer (OR, 11.1; 95% Cl, 2.2-54.9). Logistic regression models for HPV 16 and for HPV 18 viral load levels were significant, with higher viral load associated with cervical abnormalities. These findings indicate that viral load is a predictor significantly associated with cytology abnormality in women who are positive for high-risk HPVs and suggest that integrating a viral load test into current clinical screening practices for HPV-positive women is warranted in Saudi Arabia.

show abstract

“…E2 binds to specific sequence motifs in the viral genome as determined by binding of these sequences to the DNA binding domain of E2, GST-E2 fusion protein, as well as purified full-length E2 proteins [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. DNA replication initiation is well studied in E. coli , where DnaA binds to four nine bp recognition sites in the 245 bp region of the E. coli DNA replication origin [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Sequence-Dependent Interaction of the Human Papillomavirus E2 Protein with the DNA Elements on Its DNA Replication Origin

Yılmaz

Biswas-Fiss

Biswas

2023

IJMS

Self Cite

View full text Add to dashboard Cite

The human papillomavirus (HPV) E2 protein is essential for regulating the initiation of viral DNA replication as well as the regulation of transcription of certain HPV-encoded genes. Its ability to recognize and bind to its four recognition sequences in the viral origin is a key step in the initiation of HPV DNA replication. Thus, understanding the mechanism of DNA binding by E2 protein and the unique roles played by individual DNA sequence elements of the replication origin is essential. We have purified the recombinant full-length HPV type 11 E2 protein. Quantitative DNA binding analysis indicated E2 protein bound all four DNA binding sites with reasonably high affinities but with distinct preferences. It bound its cognate binding sites 1, 2, and 4 with higher affinities, but bound binding site 3 with lower affinity. Analysis of binding to these sites unraveled multiple sequence elements that appeared to influence E2 binding affinity and target discrimination, including the sequence of spacer region, flanking sequences, and proximity of E2 binding sites. Thermodynamic analysis indicated hydrophobic interaction in the protein-DNA complex formation. Our studies indicate a large multi-protein complex formation on the HPV-origin DNA, likely due to reasonably high binding affinities as well as intrinsic oligomerization propensity of E2 dimers.

show abstract

Genetic variations in the DNA replication origins of human papillomavirus family correlate with their oncogenic potential

Cited by 8 publications

References 50 publications

Prevalence and Genotype Distribution of Human Papillomavirus Among Attendees at a Sexually Transmitted Diseases Clinic in Urban Tianjin, China

Prevalence and Genotype Distribution of Human Papillomavirus Among Attendees at a Sexually Transmitted Diseases Clinic in Urban Tianjin, China

Human papillomavirus type 16 and 18 viral loads as predictors associated with abnormal cervical cytology among women in Saudi Arabia

Sequence-Dependent Interaction of the Human Papillomavirus E2 Protein with the DNA Elements on Its DNA Replication Origin

Contact Info

Product

Resources

About