scholarly journals The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 786
Author(s):  
Ryan T. Gibson ◽  
Elliot J. Androphy
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Viral Replication ◽  
Chromatin Immunoprecipitation ◽  
Binding Sites ◽  
Viral Infections ◽  
Hpv Infection ◽  
Regulatory Proteins ◽  
Transactivation Domain ◽  
Structural Maintenance Of Chromosomes

The multi-subunit structural maintenance of chromosomes (SMC) 5/6 complex includes SMC6 and non-SMC element (NSE)3. SMC5/6 is essential for homologous recombination DNA repair and functions as an antiviral factor during hepatitis B (HBV) and herpes simplex-1 (HSV-1) viral infections. Intriguingly, SMC5/6 has been found to associate with high-risk human papillomavirus (HPV) E2 regulatory proteins, but the functions of this interaction and its role during HPV infection remain unclear. Here, we further characterize SMC5/6 interactions with HPV-31 E2 and its role in the HPV life cycle. Co-immunoprecipitation (co-IP) revealed that SMC6 interactions with HPV-31 E2 require the E2 transactivation domain, implying that SMC5/6 interacts with full-length E2. Using chromatin immunoprecipitation, we found that SMC6 is present on HPV-31 episomes at E2 binding sites. The depletion of SMC6 and NSE3 increased viral replication and transcription in keratinocytes maintaining episomal HPV-31, indicating that SMC5/6 restricts the viral replicative program. SMC6 interactions with E2 were reduced in the presence of HPV-31 E1, suggesting that SMC6 and E1 compete for E2 binding. Our findings demonstrate SMC5/6 functions as a repressor of the viral replicative program and this may involve inhibiting the initiation of viral replication.

scholarly journals High Risk Human Papillomavirus genital infections in asymptomatic population: effectiveness of Micro-Immunotherapy

2021 ◽  
Vol 11 (40) ◽  
pp. 134-135
Author(s):  
Sandra Mazzoli ◽  
Tommaso Cai ◽  
Francesca Meacci ◽  
Patrizia Addonisio ◽  
Pierre Dorfman
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Viral Infections ◽  
Interleukin 1 ◽  
Interleukin 2 ◽  
Hpv Infection ◽  
Exact Test ◽  
Hpv Dna ◽  
Asymptomatic Patients

Background: persistent infection with high-risk human papillomavirus (HR-HPV) is the primary cause for the development of various anogenital cancers in females and males. Most infections are either latent or subclinical and the majority occur as asymptomatic. HPV infections are not currently treatable by antiviral compounds. Micro-immunotherapy (MI) medications using high dilutions of cytokines and specific nucleotide sequences have been developed to treat targeted viral infections and are currently prescribed in medical practice as immune regulators: 2L®PAPI (Labo’Life) is indicated for HPV infection and may represent a new therapeutic approach. Aims: this exploratory study was to assess the effectiveness of 2L®PAPI on HPV infection eradication in HR-HPV infected asymptomatic patients attending an STD Centre in a long-term microbiological follow-up population survey. Methodology: adult patients of both genders, diagnosed with HR-HPV infection, with no evidence of symptomatic HPV or anogenital cancer, were followed during a 2 year-period (2009-2010). Selected patients had not previously been vaccinated for HPV or treated with medications having an impact on the immune system. HPV testing was performed on biological samples using PCR detection (Innogenetics, Italy). In addition, detection of E6/E7 mRNA of five carcinogenic HPV types was performed by EasyQ HPV (BioMerieux, Italy). HPV-positives were requested by their urology specialist to take 2L®PAPI (composition in table 1) during 4 months (1 caps/day by sublingual route). Globally 46 patients were followed: 23 treated with MI medication, and 23 not treated. Results: one third of selected patients were lost at the control visit (15/46). At the end of the study period, HR-HPV negativity was observed in 50% (8/16) of patients under MI medication in comparison with only 7% (1/15) of the non treated patients who were HPV-DNA negative at the follow-up visit (p=0.01071, Mid-P exact test). This result is in accordance with our previous results which showed long lasting persistence of HR-HPV infection in a male cohort. Conclusions: the relevant percentage of lost patients at follow-up reflects the scarce information and awareness of this infection within asymptomatic people in Italy. 2L®PAPI was efficient in eradicating 50% of HR-HPV infections in treated patients, including 60% of HPV-16. These promising data emphasize the importance of redirecting immune responses in viral infections. Table 1: 2L®PAPI composition Compounds Dilutions Interleukin-1 (IL-1): 17-10 CH* Interleukin-2 (IL-2): 17-10 CH Interferon-α (IFN-α): 17-10 CH SNA-HLA II: 16-10 CH Ciclosporin A (CsA): 7-10-17 CH Ribonucleic acid (RNA): 18-10 CH SNA-PAPI: 16-10 CH * CH: Centesimal Hahnemannian (1/100)

scholarly journals Molecular characterization of high-risk human papillomavirus (HR-HPV) in women in Lomé, Togo

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Akouélé P. Kuassi-Kpede ◽  
Essolakina Dolou ◽  
Théodora M. Zohoncon ◽  
Ina Marie Angèle Traore ◽  
Gnatoulma Katawa ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
West Africa ◽  
Public Health Problem ◽  
Hpv Infection ◽  
Cervical Lesions ◽  
Hpv Genotypes ◽  
Precancerous Cervical Lesions ◽  
High Risk Hpv ◽  
First Time

Abstract Background The causative agent of cervical cancer referred to as Human papillomavirus (HPV) remains a real public health problem. Many countries in West Africa, such as Togo have no data on the high-risk HPV (HR-HPV) infection and genotypes distribution. In order to fill the knowledge gap in the field in Togo, the main objective of this study was to determine the prevalence of pre-cancerous lesions of the cervix and HR-HPV genotypes among Togolese women. Methods Samples were collected from 240 women by introducing a swab in the cervix. Then, the screening of precancerous cervical lesions using the visual inspection with acetic acid and lugol (VIA / VIL) was conducted. The HR-HPV genotypes were characterised by real-time multiplex PCR. Results Out of 240 women recruited, 128 (53.3%) were infected by HR-HPV. The most common genotypes were HPV 56 (22.7%), followed by HPV 51 (20.3%), HPV 31 (19.5%), HPV 52 (18.8%) and HPV 35 (17.2%). The least common genotypes were HPV 33 (2.3%) and HPV 16 (2.3%). Among the women, 1.3% (3/240) were positive to VIA/VIL. Conclusion This study allowed HR-HPV genotypes to be characterised for the first time in Lomé, Togo. This will help in mapping the HR-HPV genotypes in West Africa.

scholarly journals High-Risk Human Papillomavirus and Tobacco Smoke Interactions in Epithelial Carcinogenesis

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2201 ◽  
Author(s):  
Francisco Aguayo ◽  
Juan P. Muñoz ◽  
Francisco Perez-Dominguez ◽  
Diego Carrillo-Beltrán ◽  
Carolina Oliva ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Tobacco Smoke ◽  
Molecular Mechanisms ◽  
Complex Mixture ◽  
Epidemiological Studies ◽  
Hpv Infection ◽  
Oncogenic Viruses ◽  
Cancer Initiation ◽  
Physical Environmental Factors

Cervical, anogenital, and some head and neck cancers (HNC) are etiologically associated with high-risk human papillomavirus (HR-HPV) infection, even though additional cofactors are necessary. Epidemiological studies have established that tobacco smoke (TS) is a cofactor for cervical carcinogenesis because women who smoke are more susceptible to cervical cancer when compared to non-smokers. Even though such a relationship has not been established in HPV-related HNC, a group of HPV positive patients with this malignancy are smokers. TS is a complex mixture of more than 4500 chemical compounds and approximately 60 of them show oncogenic properties such as benzo[α]pyrene (BaP) and nitrosamines, among others. Some of these compounds have been evaluated for carcinogenesis through experimental settings in collaboration with HR-HPV. Here, we conducted a comprehensive review of the suggested molecular mechanisms involved in cooperation with both HR-HPV and TS for epithelial carcinogenesis. Furthermore, we propose interaction models in which TS collaborates with HR-HPV to promote epithelial cancer initiation, promotion, and progression. More studies are warranted to clarify interactions between oncogenic viruses and chemical or physical environmental factors for epithelial carcinogenesis.

scholarly journals Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus(HPV) Infection

2019 ◽  
Author(s):  
Sally N. Adebamowo ◽  
Adebowale A Adeyemo ◽  
Charles N Rotimi ◽  
Olayinka Olaniyan ◽  
Richard B. Offiong ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Principal Component ◽  
Hpv Infection ◽  
Genome Wide Association ◽  
Replication Studies ◽  
Genome Wide

Abstract Background: Genetic factors may influence the susceptibility to high-risk human papillomavirus (hrHPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. Methods: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. Results: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p=1.43 x 10-6). The top variants associated with cervical hrHPV persistence were in DAP(OR: 6.86, p=7.15 x 10-8), NR5A2(OR: 3.65, p=2.03 x 10-7) and MIR365-2(OR: 7.71, p=2.63 x 10-7) gene regions. Conclusions: This exploratory GWAS yielded novel candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

The genomic distribution map of human papillomavirus in China

2021 ◽  
Author(s):  
Ling Chen ◽  
Yan Dong ◽  
Jiao Li ◽  
Jinqiu Zhao ◽  
Li Xu ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Infection Rate ◽  
Subgroup Analysis ◽  
Hpv Infection ◽  
Single Type ◽  
Distribution Map ◽  
Double Infection ◽  
Genomic Distribution ◽  
High Risk Hpv

Abstract In this study, a total of 301,880 woman were recruited from 4 different regions of China. The overall prevalence of HPV was 18.01 %. The high-risk HPV infection rate was 79.14%, the low-risk HPV infection rate was 12.56 %, and the mixed HPV infection rate was 8.30%. The most common 4 HR HPV subtypes were HPV-52, 16, 58 and 53, which accounted for 20.49 %, 19.93 %, 14.54 % and 10.01 %. In LR HPV genotype, HPV-6 ranked the highest (28.17 %), followed by HPV-81 (9.09 %) and HPV-11 (3.78 %). HPV genotype subgroup analysis also showed that single-type infections had the highest prevalence rate (77.26 %) among HPV positive individuals. Among muti-infection genotype, double infection was the most common with frequencies of 76.04 %. This large report showed that the overall prevalence of HPV was high in China, whose distribution exhibits different patterns across different particular age and regions. Viral genotypes HPV 53, 6 were frequently detected in this population, which is worth of significant clinical attention.

Characteristics of high-risk human papillomavirus infection in women with abnormal cervical cytology: a population-based study in Shanxi Province, China

2019 ◽  
Author(s):  
Li Song ◽  
Yuanjing Lyu ◽  
Ling Ding ◽  
Xiaoxue Li ◽  
Wen Gao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Hpv Infection ◽  
Cervical Cytology ◽  
Shanxi Province ◽  
Low Grade ◽  
Squamous Intraepithelial Lesion ◽  
Abnormal Cervical Cytology ◽  
Intraepithelial Lesion

Abstract Background: High-risk human papillomavirus (HR-HPV) infection is widely known as the major cause of cervical intraepithelial neoplasia (CIN) and cervical cancer and it’s characteristics vary greatly in different population. Women with abnormal cervical cytology could increase the risk of cervical cancer, however, HR-HPV infection characteristics in women with abnormal cervical cytology remains unclear. Methods: This study was based on baseline survey of the CIN Cohort established in Shanxi Province, China. A total number of 2300 women with cervical abnormalities were enrolled in this study. All participants gave informed consent and agreed to HPV and thinprepcytologic test (TCT). Each individual completed a questionnaire about characteristics related to HPV infection. Results: The overall prevalence of HR-HPV in 2300 women was 32.0%, and the proportion of single and multiple HR-HPV infections were 70.2% and 29.8% in HR-HPV infection women, respectively. The top five HR-HPV genotypes were ranked as HPV16, HPV58, HPV52, HPV53 and HPV51. The prevalence of HR-HPV in atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion and above(HSIL+) were 30.8%, 36.5% and 54.9%, respectively, showing an increasing trend with the severity of cervical cytology ( χ 2 trend =13.952; p <0.001). The women aged 35~45 years, with lower education level, less frequency of bathing, multiple gravidity, multiple parity, history of gynecological diseases and premenopausal women were prone to HR-HPV infection. Conclusions: We defined the characteristics related to HR-HPV infection in abnormal cervical cytology women, and provided an insight for the development and deeply research of HPV vaccine.

Carriage of high-risk human papillomavirus infection in male subjects in Ouagadougou, Burkina Faso

2019 ◽  
Author(s):  
Sya Forazoun Bienvenue Tamini ◽  
Theodora Mahoukèdè Zohoncon ◽  
Serge Theophile Soubeiga ◽  
Florencia Wendkuuni Djigma ◽  
Ina Marie Angele Traore ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Burkina Faso ◽  
Public Health Problem ◽  
Hpv Infection ◽  
Cross Sectional Study ◽  
Multiple Infections ◽  
Cross Sectional ◽  
High Risk Hpv ◽  
Male Subjects

Abstract Background Human papillomavirus (HPV) infection is a public health problem in Africa because of its frequency and its various consequences in both men and women. In Burkina Faso, there is little data on the carriage of HPV infection in male subjects. This study aimed to determine the carriage of HPV infection in male subjects in Ouagadougou, Burkina Faso.Methods This was a cross-sectional study conducted from December 2015 to September 2016. During this study period, a total of 124 male subjects who gave informed consent were recruited as part of a fertility assessment. Semen samples were analyzed by Real- Time PCR using Real TM Quant High Risk Screen HPV kit to detect 14 high-risk HPV genotypes. The Chi square test was used for comparisons.Results Of the 124 male subjects, 22 were positive for at least one high-risk HPV, with a prevalence of 17.7%. HPV 56 was the most represented genotype with a frequency of 20%, followed by HPV 39 (11%) and HPV 68 (11%), HPV 16 (8%). The genotypes HPV 18, HPV33, HPV35, HPV51 and HPV52 also had the same frequency of 6% each and the HPV 31, 45, 59 and 66 had the same frequency of 3% each. Of the 22 positive cases, 10 were multiple infections. Spermocytogram of patients showed at least one abnormality in 87.9% of cases. Necrozoospermia and oligozoospermia were the most abnormalities observed with 42% and 40% respectively followed by asthenospermia (18%); teratozoospermia (16%) and azoospermia (14%).Conclusion This study showed that like women, men are infected by HPV with a relatively high prevalence. In addition, the predominant genotypes in the male subjects of this study are not those targeted by the HPV vaccines available in our countries. Hence the need to reinforce the strategies for controlling HPV infection and HPV prophylactic vaccination for young boys.

Prevalence and Genotype distribution of Human Papillomavirus Infection in Different Anatomical Sites among Men Who Have Sex with Men (MSM): A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Mohammad Farahmand ◽  
Seyed Hamidreza Monavari ◽  
Ahmad Tavakoli
Keyword(s):  
Systematic Review ◽  
Human Papillomavirus ◽  
High Risk ◽  
Sexual Behaviors ◽  
Meta Analysis ◽  
Hpv Infection ◽  
Genotype Distribution ◽  
Increased Risk ◽  
Pertinent Data ◽  
Sex With Men

Abstract Background: Homosexual men or men who have sex with men (MSM) are at increased risk of human papillomavirus (HPV) infection because of their high-risk sexual behaviors. In this large study, a meta-analytic approach was used to systematically analyze the literature to elucidate the prevalence and genotype distribution of anal, penile, oral, and urethral HPV infection among MSM in the world.Methods: To carry out this systematic review, five electronic databases were searched for relevant studies published from January 2012 through to November 2019, and pertinent data were collected from the eligible articles. The pooled HPV prevalences were calculated for each anatomical region using random-effect model weighted by the inverse variance method. Subgroup analyses were performed to identify the probable sources of heterogeneity. The meta-analysis was performed using the “Metaprop” function in the R package Meta.Results: The overall pooled prevalence of anal, penile, oral, and urethral HPV infection among MSM were 78.11 % (95% CI: 75.50%-80.52%), 36.26% (95% CI: 29.13%–44.05%), 17.33% (95% CI: 13.65%–21.75%), and 15.40% (95% CI: 7.86%–27.97%), respectively. Stratified analyses showed that the prevalences of HPV were significantly higher in HIV-positive than HIV-negative MSM. The most frequent HPV high-risk type detected in the anus, penis, and oral cavity was HPV-16 (20.32%, 4.96%, and 3.16%, respectively). Conclusion: HPV infection is on the dramatic rise in MSM because of high-risk sexual behaviors, strongly suggesting the increased risk of developing HPV-related diseases and malignancies in this population. Among different sexual orientations, male homosexuality is associated with the highest risk of acquiring sexually transmitted infections.

A systematic review and meta-analysis of the association between periodontitis and oral high-risk human papillomavirus infection

2020 ◽  
Author(s):  
Anna Ali ◽  
Zohra S Lassi ◽  
Kostas Kapellas ◽  
Lisa Jamieson ◽  
Alice R Rumbold
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Confidence Interval ◽  
Meta Analysis ◽  
Positive Association ◽  
Hpv Infection ◽  
Eligibility Criteria ◽  
Oral Hpv ◽  
Meta Analyses

Abstract Background The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is increasing globally. Common oral conditions such as periodontitis may contribute. We undertook a meta-analysis to quantify the association between periodontitis, oral HPV and OPSCCs. Methods Multiple electronic databases were searched until 12 February 2020. Studies conducted in males and/or females aged ≥ 18 years that examined periodontitis, periodontal procedures, oral HPV infection, and where possible, oral cancers, were eligible. Meta-analyses were conducted and the GRADE approach was used to examine the quality of evidence. Results Of 2709 studies identified, 13 met the eligibility criteria. Five studies could be included in the meta-analyses. There was no significant increase in the odds of high-risk oral HPV infection among individuals with confirmed periodontitis (odds ratio 4.71, 95% confidence interval 0.57–38.97). Individuals with periodontitis had a 3.65 times higher odds of having any type of oral HPV infection compared with those without periodontitis (95% confidence interval 1.67–8.01). The overall body of evidence was rated as low to very-low certainty. Conclusion Meta-analysis confirms there is a positive association between periodontitis and oral HPV infection, although the overall quality of this evidence is low. Evidence for an association between periodontitis and high-risk oral HPV infection is inconclusive.

scholarly journals Neutralization of Human Papillomavirus with Monoclonal Antibodies Reveals Different Mechanisms of Inhibition

2007 ◽  
Vol 81 (16) ◽  
pp. 8784-8792 ◽  
Author(s):  
Patricia M. Day ◽  
Cynthia D. Thompson ◽  
Christopher B. Buck ◽  
Yuk-Ying S. Pang ◽  
Douglas R. Lowy ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Monoclonal Antibodies ◽  
Human Papillomavirus ◽  
Cell Surface ◽  
Binding Sites ◽  
Neutralizing Antibodies ◽  
Hpv Infection ◽  
Heparan Sulfate Proteoglycans ◽  
Hacat Cells ◽  
Block Association

ABSTRACT The mechanisms of human papillomavirus (HPV) neutralization by antibodies are incompletely understood. We have used HPV16 pseudovirus infection of HaCaT cells to analyze how several neutralizing monoclonal antibodies (MAbs) generated against HPV16 L1 interfere with the process of keratinocyte infection. HPV16 capsids normally bind to both the cell surface and extracellular matrix (ECM) of HaCaT cells. Surprisingly, two strongly neutralizing MAbs, V5 and E70, did not prevent attachment of capsids to the cell surface. However, they did block association with the ECM and prevented internalization of cell surface-bound capsids. In contrast, MAb U4 prevented binding to the cell surface but not to the ECM. The epitope recognized by U4 was inaccessible when virions were bound to the cell surface but became accessible after endocytosis, presumably coinciding with receptor detachment. Treatment of capsids with heparin, which is known to interfere with binding to cell surface heparan sulfate proteoglycans (HSPGs), also resulted in HPV16 localization to the ECM. These results suggest that the U4 epitope on the intercapsomeric C-terminal arm is likely to encompass the critical HSPG interaction residues for HPV16, while the V5 and E70 epitopes at the apex of the capsomer overlap the ECM-binding sites. We conclude that neutralizing antibodies can inhibit HPV infection by multiple distinct mechanisms, and understanding these mechanisms can add insight to the HPV entry processes.

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