scholarly journals Sp100 Provides Intrinsic Immunity against Human Papillomavirus Infection

mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Wesley H. Stepp ◽  
Jordan M. Meyers ◽  
Alison A. McBride
Keyword(s):  
Human Papillomavirus ◽  
Dna Replication ◽  
Human Keratinocytes ◽  
Hpv Infection ◽  
Nuclear Bodies ◽  
Host Cells ◽  
Viral Transcription ◽  
Primary Human Keratinocytes ◽  
Dna Viruses ◽  
Hpv Dna

ABSTRACTMost DNA viruses associate with, and reorganize, nuclear domain 10 (ND10) bodies upon entry into the host nucleus. In this study, we examine the roles of the ND10 components PML, Sp100, and Daxx in the establishment of human papillomavirus type 18 (HPV18) infection of primary human keratinocytes. HPV18 DNA or HPV18 quasivirus was introduced into primary human keratinocytes depleted of each ND10 protein by small interfering RNA technology, and genome establishment was determined by using a quantitative immortalization assay and measurements of viral transcription and DNA replication. Keratinocyte depletion of Sp100 resulted in a substantial increase in the number of HPV18-immortalized colonies and a corresponding increase in viral transcription and DNA replication. However, Sp100 repressed viral transcription and replication only during the initial stages of viral establishment, suggesting that Sp100 acts as a repressor of incoming HPV DNA.IMPORTANCEThe intrinsic immune system provides a first-line defense against invading pathogens. Host cells contain nuclear bodies (ND10) that are important for antiviral defense, yet many DNA viruses localize here upon cell entry. However, viruses also disrupt, reorganize, and modify individual components of the bodies. In this study, we show that one of the ND10 components, Sp100, limits the infection of human skin cells by human papillomavirus (HPV). HPVs are important pathogens that cause many types of infection of the cutaneous and mucosal epithelium and are the causative agents of several human cancers. Understanding how host cells counteract HPV infection could provide insight into antimicrobial therapies that could limit initial infection.

scholarly journals Expression of membrane type 1 matrix metalloproteinase in papillomavirus-positive cells: role of the human papillomavirus (HPV) 16 and HPV8 E7 gene products

2005 ◽  
Vol 86 (5) ◽  
pp. 1291-1296 ◽  
Author(s):  
Sigrun Smola-Hess ◽  
Jenny Pahne ◽  
Cornelia Mauch ◽  
Paola Zigrino ◽  
Hans Smola ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cellular Proliferation ◽  
Human Keratinocytes ◽  
Hpv Infection ◽  
Host Cells ◽  
Primary Human Keratinocytes ◽  
E7 Gene ◽  
Membrane Type

Matrix metalloproteinases (MMPs) degrade extracellular matrix. They are involved in cellular proliferation, migration, angiogenesis, invasion and metastasis. MT-1 MMP, a membrane-bound MMP, is expressed in carcinomas of the uterine cervix in vivo. This type of cancer is associated with human papillomavirus (HPV) infection. Here it was shown that keratinocytes transformed with HPV16 or HPV18 in vitro, and HPV-positive cervical carcinoma cell lines, constitutively expressed MT-1 MMP. Expression of the E7 protein from the mucosal and cutaneous high-risk types HPV16 and HPV8, but not from the cutaneous low-risk type HPV1, was sufficient to induce MT-1 MMP expression in primary human keratinocytes and HaCaT cells. As a consequence, MMP-2 was activated. MT-1 MMP expression might play a role in the HPV life cycle by promoting proliferation of host cells and might contribute to their invasive phenotype during malignant progression.

scholarly journals p21cip1 Degradation in Differentiated Keratinocytes Is Abrogated by Costabilization with Cyclin E Induced by Human Papillomavirus E7

2001 ◽  
Vol 75 (13) ◽  
pp. 6121-6134 ◽  
Author(s):  
Francisco Noya ◽  
Wei-Ming Chien ◽  
Thomas R. Broker ◽  
Louise T. Chow
Keyword(s):  
Human Papillomavirus ◽  
Dna Replication ◽  
Cyclin E ◽  
Human Keratinocytes ◽  
S Phase ◽  
Brdu Incorporation ◽  
Primary Human Keratinocytes ◽  
Differentiated Cells ◽  
Hpv E7 ◽  
Cyclin E2

ABSTRACT The human papillomavirus (HPV) E7 protein promotes S-phase reentry in a fraction of postmitotic, differentiated keratinocytes. Here we report that these cells contain an inherent mechanism that opposes E7-induced DNA replication. In organotypic raft cultures of primary human keratinocytes, neither cyclin E nor p21cip1 is detectable in situ. However, E7-transduced differentiated cells not in S phase accumulate abundant cyclin E and p21cip1. We show that normally p21cip1 protein is rapidly degraded by proteasomes. In the presence of E7 or E6/E7, p21cip1, cyclin E, and cyclin E2 proteins were all up-regulated. The accumulation of p21cip1 protein is a posttranscriptional event, and ectopic cyclin E expression was sufficient to trigger it. In constract, cdk2 and p27kip1 were abundant in normal differentiated cells and were not significantly affected by E7. Cyclin E, cdk2, and p21cip1 or p27kip1 formed complexes, and relatively little kinase activity was found associated with cyclin E or cdk2. In patient papillomas and E7 raft cultures, all p27kip1-positive cells were negative for bromodeoxyuridine (BrdU) incorporation, but only some also contained cyclin E and p21cip1. In contrast, all cyclin E-positive cells also contained p27kip1. When the expression of p21cip1 was reduced by rottlerin, a PKC δ inhibitor, p27kip1- and BrdU-positive cells remained unchanged. These observations show that high levels of endogenous p27kip1 can prevent E7-induced S-phase reentry. This inhibition then leads to the stabilization of cyclin E and p21cip1. Since efficient initiation of viral DNA replication requires cyclin E and cdk2, its inhibition accounts for heterogeneous viral activities in productively infected lesions.

scholarly journals Genetic Analysis of High-Risk E6 in Episomal Maintenance of Human Papillomavirus Genomes in Primary Human Keratinocytes

2002 ◽  
Vol 76 (22) ◽  
pp. 11359-11364 ◽  
Author(s):  
Regina B. Park ◽  
Elliot J. Androphy
Keyword(s):  
Human Papillomavirus ◽  
Dna Replication ◽  
High Risk ◽  
Viral Replication ◽  
Human Keratinocytes ◽  
Binding Motif ◽  
Primary Human Keratinocytes ◽  
Hpv16 E6 ◽  
E6 And E7 ◽  
Episomal Maintenance

ABSTRACT Papillomaviruses possess small DNA genomes that encode five early (E) proteins. Transient DNA replication requires activities of the E1 and E2 proteins and a DNA segment containing their binding sites. The E6 and E7 proteins of cancer-associated human papillomavirus (HPV) transform cells in culture. Recent reports have shown that E6 and E7 are necessary for episomal maintenance of HPV in primary keratinocytes. The functions of E6 necessary for viral replication have not been determined, and to address this question we used a recently developed transfection system based on HPV31. To utilize a series of HPV16 E6 mutations, HPV31 E6 was replaced by its HPV16 counterpart. This chimeric genome was competent for both transient and stable replication in keratinocytes. Four HPV16 E6 mutations that do not stimulate p53 degradation were unable to support stable viral replication, suggesting this activity may be necessary for episomal maintenance. E7 has also been shown to be essential for episomal maintenance of the HPV31 genome. A point mutation in the Rb binding motif of HPV E7 has been reported to render HPV31 unable to stably replicate. Interestingly, HPV31 genomes harboring two of the three p53 degradation-defective E6 mutations combined with this E7 mutation were maintained as replicating episomes. These findings imply that the balance between E6 and E7 functions in infected cells is critical for episomal maintenance of high-risk HPV genomes. This model will be useful to dissect the activities of E6 and E7 necessary for viral DNA replication.

scholarly journals Prevalence and genotype distribution of human papillomavirus in Czech non-vaccinated heterosexual couples

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Hana Jaworek ◽  
Vladimira Koudelakova ◽  
Ivana Oborna ◽  
Blazena Zborilova ◽  
Jana Brezinova ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Hpv Infection ◽  
Sexual Partners ◽  
Fisher Exact Test ◽  
Genotype Distribution ◽  
Heterosexual Couples ◽  
Anatomic Site ◽  
Hpv Dna ◽  
Hpv Test ◽  
Penile Swabs

Abstract Background Data about the genotype-specific human papillomavirus (HPV) prevalence in the Czech Republic is limited. We aimed to evaluate the prevalence and concordance of genotype-specific HPV infection detected in semen samples, penile swabs and cervical swabs from non-vaccinated heterosexual couples without HPV-associated disease. Methods Semen samples and penile swabs were collected from male partners and cervical swabs were collected from female partners of heterosexual couples treated for infertility (n = 195). Presence of HPV DNA in semen samples and cervical swabs was analyzed using the cobas® HPV Test and PapilloCheck®. Only the PapilloCheck® test was used to detect HPV in penile swabs. The genotype-specific prevalence and concordance of HPV infection not targeted by vaccine were evaluated using Fisher exact test. Results Both partners were infected with any HPV type in 13.8% (27/195) of couples and, of these couples, 55.6% (15/27) harbored at least one mutual genotype. High-risk HPV (hrHPV) genotypes were detected in 12.3% (24/195) of semen samples, 31.3% (61/195) of penile swabs, and 19.5% (38/195) of cervical swabs (P < 0.001). The most prevalent hrHPV genotype were HPV53 (2.56%; 5/195) in semen samples, HPV16 (6.67%, 13/195) in penile swabs and HPV39 (3.59%, 7/195) in cervical swabs. Low-risk (lrHPV) genotypes were detected in 5.13% (10/195) of semen samples, 15.9% (31/195) of penile swabs, and 4.10% (8/195) of cervical swabs (P < 0.001). Male sexual partners of HPV-positive women were more likely to be infected with at least one of the same HPV types than female sexual partners of HPV-positive men (34.9% vs. 17.9%, P = 0.055). Conclusions This study showed that the detection of HPV infection differ by anatomic site and gender. Regardless the anatomic site, high prevalence of HPV genital infection was found in both Czech men and women.

scholarly journals Triage of human papillomavirus infected women by methylation analysis in first-void urine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Severien Van Keer ◽  
Annina P. van Splunter ◽  
Jade Pattyn ◽  
Annemie De Smet ◽  
Sereina A. Herzog ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Host Cell ◽  
Intraepithelial Neoplasia ◽  
Underlying Disease ◽  
Hpv Infection ◽  
Molecular Testing ◽  
High Grade ◽  
Methylation Analysis ◽  
Hpv Dna ◽  
Screening Attendance

AbstractHost cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59–0.92) and 0.76 (95% CI 0.58–0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.

The role of circumcision, tobacco, and alcohol use in genital human papillomavirus infection among men from Denmark

2021 ◽  
pp. 095646242110147
Author(s):  
Julie B Hebnes ◽  
Christian Munk ◽  
Kirsten Frederiksen ◽  
Hans O Joergensen ◽  
Thomas Iftner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sexual Behavior ◽  
Human Papillomavirus ◽  
Alcohol Use ◽  
Potential Risk ◽  
Hpv Infection ◽  
Sex Partners ◽  
Current Cigarette Smoking ◽  
Hpv Dna ◽  
Potential Risk Factors

It is crucial to understand the natural history of genital human papillomavirus (HPV) infection in men to prevent the increasing male HPV-related disease burden. We evaluated the associations between HPV infection and circumcision, smoking, and alcohol use after accounting for sexual behavior. The study included 2331 male personnel from Danish barracks. Penile swabs were tested for HPV DNA with a polymerase chain reaction assay, INNO-LiPA. All men completed a self-administered questionnaire providing data on potential risk factors for HPV such as lifestyle and sexual habits. Using multivariable logistic regression, associations between potential risk factors and HPV infection were estimated and expressed as odds ratios (ORs) with 95% confidence intervals (CI). Current cigarette smoking was associated with increased odds of HPV detection (OR = 1.2; 95% CI: 1.0–1.4), but we found no association with alcohol use in the analysis adjusted for sexual behavior. Circumcision reduced the odds of a prevalent HPV infection (OR = 0.7; 95% CI: 0.5–1.0) although not statistically significantly. Strong associations with lifetime and recent number of female sex partners were observed, but in contrast to uncircumcised men, increasing number of sex partners was not associated with higher HPV prevalence in circumcised men. In conclusion, smoking was associated with increased odds of penile HPV in men from the general population in Denmark, whereas circumcision seemed to reduce the risk. Moreover, our results indicated that there might be differences in the viral susceptibility between circumcised and uncircumcised men.

scholarly journals Distribution and Prevalence of High-Risk Human Papillomavirus Genotypes in Cervical Specimens

2020 ◽  
Vol 25 (3) ◽  
pp. 325-331
Author(s):  
Erkan Özmen ◽  
Ülkü Altoparlak ◽  
Muhammet Hamidullah Uyanık ◽  
Abdulkadir Gülen
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Age Groups ◽  
Hpv Infection ◽  
High Rate ◽  
Genotype Distribution ◽  
Hpv Dna ◽  
Hpv Test ◽  
Significant Difference ◽  
Hpv Types

Introduction: Human papillomavirus (HPV) is frequently a sexually transmitted virus and can cause cervical cancer in women. Cervical cancer is the second most common type of cancer among the developing countries. In this study, cervical HPV DNA positivity and genotype distributions were investigated in female patients living in our region and the results were compared with different studies. Materials and Methods: Between 1 July, 2017 and 1 March, 2019, 433 cervical swabs were sent to Ataturk University, Medical Faculty Hospital, Medical Microbiology Laboratory due to suspicion of HPV. Swab samples were evaluated for HPV virus using molecular (Polymerase Chain Reaction-PCR) methods. For this purpose, Xpert HPV Test (Cepheid, Inc, Sunnyvale, CA) was used to identify HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 t in a single sample. Results: Mean age of the patients ranged from 20 to 69 years, with a mean of 39.8 years (± 10.0). Positivity was detected in 62 of the 433 patients. Mean age of the positive patients was 40.2 years (± 11.3). When the positive patients were examined in terms of HPV types, the presence of HPV 16 was observed with a rate of 25.6%, while the HPV 18/45 types were found to be 9.0% in total. When patients were evaluated according to age groups, HPV DNA positivity was highest in the 25-34 age group with 38.7%. In our statistical study, there was no significant difference in HPV DNA positivity rate between the ages of 35 and under 35 years. Conclusion: This study demonstrates the prevalence and viral genotype distribution of HPV infection in women in Erzurum region. HPV type 16 is seen with a high rate in our region.

Self-sampling versus physician-sampling for human papillomavirus testing

2005 ◽  
Vol 16 (11) ◽  
pp. 727-729 ◽  
Author(s):  
T Agorastos ◽  
K Dinas ◽  
B Lloveras ◽  
R Font ◽  
JR Kornegay ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Sampling Methods ◽  
Cervical Dysplasia ◽  
Kappa Statistic ◽  
Hpv Infection ◽  
Outpatient Clinics ◽  
Sampling Techniques ◽  
Northern Greece ◽  
Hpv Dna ◽  
Exfoliated Cells

We evaluated the detection of human papillomavirus (HPV) infection using two sampling methods of cervical exfoliated cells, consisting of self-sampling of vaginal cells and cervical sampling performed by the physician. Women included were 379 patients of the general population attending outpatient clinics in Northern Greece for routine cytological cervical dysplasia screening. HPV DNA detection was similar with both sampling techniques. The HPV prevalences in self-collected samples were 4.7% and 3.7% in the physician-collected samples ( P>0.05). The Kappa statistic for HPV DNA agreement between the two methods was 0.54 (95% Confidence interval = 0.33–0.75). Self-sampling of cervico-vaginal exfoliated cells could be used as an alternative option to test for HPV infection.

Human papillomavirus, coinfection with Schistosoma hematobium, and cervical neoplasia in rural Tanzania

2003 ◽  
Vol 13 (4) ◽  
pp. 505-509 ◽  
Author(s):  
K. U. Petry ◽  
U. Scholz ◽  
B. Hollwitz ◽  
R. Von Wasielewski ◽  
C. J.L.M. Meijer
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Invasive Cervical Cancer ◽  
Clinical History ◽  
Hpv Infection ◽  
Separate Analysis ◽  
Hpv Dna ◽  
Rural Tanzania ◽  
Increased Risk ◽  
Local Immunosuppression

Cervical cancer is the most common malignant tumor among women in Tanzania and other countries in tropical Africa. Genital schistosomiasis has been proposed as a possible cofactor in the genesis of this malignant disease that might contribute to its high incidence in regions where bilharzias is endemic. One hundred nine Tanzanian patients from an area with endemic bilharzias who were transferred to a gynecologic out-patient clinic were age-matched with 109 German controls. In patients and controls, separate samples were taken for cytologic assessment and human papillomavirus (HPV) DNA detection using the Hybrid Capture 2 assay (HC2) and PCR (GP5+/6 +). Samples that tested positive for HPV DNA with general primers were re-tested with HPV type-specific primers. After application of 3% acetic acid, punch biopsies were taken from any cervical lesion. Patients were interviewed for recent symptoms or clinical history suggestive of bilharzias. Urine samples from all patients were examined for the presence of schistosoma hematobium ova. Additionally six Tanzanian patients with invasive cervical cancer were included for separate analysis. Patients and controls had an identical prevalence of HPV-DNA (21.5%) using HC2. Based on PCR results with general primers, the corresponding prevalence was 34.5% for Tanzanian cases and 26.9% for German controls. A history suggestive of bilharzias and/or active schistosomiasis were associated with a significantly increased risk for infection with high-risk HPV types. We conclude that infection with Schistosoma hematobium seems to favor persistent genital HPV infection either by traumatizing the genital epithelium and/or by local immunosuppression.

scholarly journals Human Papillomavirus and Coronary Artery Disease in Climacteric Women: Is There an Association?

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Luciane Maria Oliveira Brito ◽  
Haissa Oliveira Brito ◽  
Rita da Graça Carvalhal Frazão Corrêa ◽  
Clariano Pires de Oliveira Neto ◽  
Joyce Pinheiro Leal Costa ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Human Papillomavirus ◽  
Coronary Artery ◽  
Sexual Behaviors ◽  
Hpv Infection ◽  
Demographic Variables ◽  
Hpv Dna ◽  
Hpv Types ◽  
Artery Disease ◽  
High Risk Hpv

Background. Cardiovascular diseases are leading causes of death worldwide. Recent studies suggest that infection by some viruses, including the human papillomavirus (HPV), may increase the risk of developing atheromatous lesions on coronary arteries. However, there is a lack of data regarding the possible association between HPV infection and coronary artery disease (CAD) in women. Objective. To investigate whether HPV infection is associated with the occurrence of CAD among climacteric women. Methods. The presence of CAD and cervical HPV DNA was investigated in 52 climacteric women. Social and demographic variables and metabolic profiles were also investigated. Results. Among 27 women with CAD, 16 were positive for HPV, whereas 11 were negative. The presence of cervical HPV was strongly associated with CAD, after adjusting for demographic variables, health and sexual behaviors, comorbidities, and known cardiovascular risk factors. HPV-positive women showed a greater likelihood of having CAD (odds ratio [OR] = 3.74; 95% confidence interval [CI]: 1.16 to 11.96) as compared with HPV-negative women, particularly those infected with high-risk HPV types (OR = 4.90; 95% CI: 1.26 to 19.08). Conclusion. These results support the hypothesis that HPV infection might be associated with CAD among climacteric women, though further studies are needed to investigate the mechanisms involved.

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