scholarly journals Human Papillomavirus Type 31b Infection of Human Keratinocytes Does Not Require Heparan Sulfate

2005 ◽  
Vol 79 (11) ◽  
pp. 6838-6847 ◽  
Author(s):  
Nicole A. Patterson ◽  
Jessica L. Smith ◽  
Michelle A. Ozbun
Keyword(s):  
High Risk ◽  
Heparan Sulfate ◽  
Human Keratinocytes ◽  
Hpv Infection ◽  
Infection Process ◽  
Human Papillomaviruses ◽  
Viral Attachment ◽  
Successful Infection ◽  
High Risk Hpv

ABSTRACT Oncogenic human papillomaviruses (HPVs) are difficult to study experimentally as they replicate at low levels in vivo. This has precluded the purification of high-risk HPV virions from in vivo lesions. Virus-like particles (VLPs) and pseudovirions from low- and high-risk HPV types can emulate various aspects of HPV virion attachment and infections. These studies suggest that HPV infection is mediated by α6-integrin and/or heparan-sulfonated receptors. However, whether VLPs and pseudovirions accurately reflect the infection process of HPV virions has not been verified. We generated infectious HPV31b virions from organotypic (raft) tissues and performed experimental infections in a variety of cells. Successful infection following viral attachment, internalization, and nuclear transport was assayed by detecting newly synthesized, spliced HPV transcripts using reverse transcription (RT)-PCR or RT-quantitative PCR. Most human epithelial cells were infected with HPV31b at a multiplicity of infection as low as 1 to 10 viral genome equivalents per cell. HPV31b infection was detected in other cell lines, including COS-7 monkey kidney cells, but higher viral multiplicities of infection were required. Heparin preparations of various molecular weights or heparinase I treatment of cells prevented HPV31b infection of COS-7 cells and C-33A human cervical cancer cells in reproducible and dose-dependent manners. However, these reagents were unable to block infection of human keratinocytes, including HaCaT and N/TERT-1 cells and low-passage human foreskin keratinocytes. These data suggest that HPV31b infection of human keratinocytes, the natural host cell for HPV infections in vivo, does not require a heparan-sulfonated receptor, whereas heparan sulfate is important for infection of some other cells.

scholarly journals HPV and Other Microbiota; Who’s Good and Who’s Bad: Effects of the Microbial Environment on the Development of Cervical Cancer—A Non-Systematic Review

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 714
Author(s):  
Matthias Läsche ◽  
Horst Urban ◽  
Julia Gallwas ◽  
Carsten Gründker
Keyword(s):  
Systematic Review ◽  
Cervical Cancer ◽  
High Risk ◽  
Cervical Carcinoma ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Inflammatory Reactions ◽  
Metabolic Signalling ◽  
Microbial Environment ◽  
High Risk Hpv

Cervical cancer is responsible for around 5% of all human cancers worldwide. It develops almost exclusively from an unsolved, persistent infection of the squamocolumnar transformation zone between the endo- and ecto-cervix with various high-risk (HR) human papillomaviruses (HPVs). The decisive turning point on the way to persistent HPV infection and malignant transformation is an immune system weakened by pathobionts and oxidative stress and an injury to the cervical mucosa, often caused by sexual activities. Through these injury and healing processes, HPV viruses, hijacking activated keratinocytes, move into the basal layers of the cervical epithelium and then continue their development towards the distal prickle cell layer (Stratum spinosum). The microbial microenvironment of the cervical tissue determines the tissue homeostasis and the integrity of the protective mucous layer through the maintenance of a healthy immune and metabolic signalling. Pathological microorganisms and the resulting dysbiosis disturb this signalling. Thus, pathological inflammatory reactions occur, which manifest the HPV infection. About 90% of all women contract an HPV infection in the course of their lives. In about 10% of cases, the virus persists and cervical intra-epithelial neoplasia (CIN) develops. Approximately 1% of women with a high-risk HPV infection incur a cervical carcinoma after 10 to 20 years. In this non-systematic review article, we summarise how the sexually and microbial mediated pathogenesis of the cervix proceeds through aberrant immune and metabolism signalling via CIN to cervical carcinoma. We show how both the virus and the cancer benefit from the same changes in the immune and metabolic environment.

scholarly journals Caveolin-1-Dependent Infectious Entry of Human Papillomavirus Type 31 in Human Keratinocytes Proceeds to the Endosomal Pathway for pH-Dependent Uncoating

2008 ◽  
Vol 82 (19) ◽  
pp. 9505-9512 ◽  
Author(s):  
Jessica L. Smith ◽  
Samuel K. Campos ◽  
Angela Wandinger-Ness ◽  
Michelle A. Ozbun
Keyword(s):  
High Risk ◽  
Human Keratinocytes ◽  
Hpv Infection ◽  
Life Cycles ◽  
Human Papillomaviruses ◽  
Endosomal Escape ◽  
Caveolin 1 ◽  
Causative Agents ◽  
Endosomal Pathway ◽  
Infectious Entry

ABSTRACT High-risk human papillomaviruses (HPVs) are small nonenveloped DNA viruses with a strict tropism for squamous epithelium. The viruses are causative agents of cervical cancer and some head and neck cancers, but their differentiation-dependent life cycles have made them difficult to study in simple cell culture. Thus, many aspects of early HPV infection remain mysterious. We recently showed the high-risk HPV type 31 (HPV31) enters its natural host cell type via caveola-dependent endocytosis, a distinct mechanism from that of the closely related HPV16 (Smith et al., J. Virol. 81:9922-9931, 2007). Here, we determined the downstream trafficking events after caveolar entry of HPV31 into human keratinocytes. After initial plasma membrane binding, HPV31 associates with caveolin-1 and transiently localizes to the caveosome before trafficking to the early endosome and proceeding through the endosomal pathway. Caveosome-to-endosome transport was found to be Rab5 GTPase dependent. Although HPV31 capsids were observed in the lysosome, Rab7 GTPase was dispensable for HPV31 infection, suggesting that viral genomes escape from the endosomal pathway prior to Rab7-mediated capsid transport. Consistent with this, the acidic pH encountered by HPV31 within the early endosomal pathway induces a conformational change in the capsid resulting in increased DNase susceptibility of the viral genome, which likely aids in uncoating and/or endosomal escape. The entry and trafficking route of HPV31 into human keratinocytes represents a unique viral pathway by which the virions use caveolar entry to eventually access a low-pH site that appears to facilitate endosomal escape of genomes.

scholarly journals The E8 Domain Confers a Novel Long-Distance Transcriptional Repression Activity on the E8^E2C Protein of High-Risk Human Papillomavirus Type 31

2001 ◽  
Vol 75 (9) ◽  
pp. 4139-4149 ◽  
Author(s):  
Frank Stubenrauch ◽  
Thomas Zobel ◽  
Thomas Iftner
Keyword(s):  
Dna Replication ◽  
High Risk ◽  
Transcriptional Repression ◽  
Viral Gene Expression ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Viral Gene ◽  
Regulation Of Transcription ◽  
Long Distance ◽  
High Risk Hpv

ABSTRACT Infections with high-risk human papillomaviruses (HPVs) are the major risk factor for the development of anogenital cancers. Viral E2 proteins are involved in viral DNA replication and regulation of transcription. Repression of the viral P97 promoter by E2 proteins has been implicated in the modulation of the immortalization capacity and DNA replication properties of high-risk HPVs. Analysis of thecis and trans requirements for repression of the HPV type 31 (HPV31) P97 promoter, however, revealed striking differences between the full-length E2 and the E8^E2C fusion protein which were due to conserved residues W6 and K7 of the E8 domain. In contrast to E2, E8^E2C completely inhibited the P97 promoter from a single promoter-distal E2 binding site. This novel long-distance repression activity of the E8 domain also enabled E8^E2C to inhibit the HPV6a P2 promoter and minimal-promoter constructs containing E2 binding sites. Thus, E8^E2C may represent the master repressor of viral gene expression during a high-risk HPV infection, and changes in the activity of E8^E2C might contribute to the progression of high-risk HPV-induced lesions.

scholarly journals Detection Rates of Human Papillomavirus Associated with Cervical Cancer in Women of Nizhny Novgorod

2020 ◽  
pp. 44-47
Author(s):  
NF Brusnigina ◽  
MA Makhova ◽  
OM Chernevskaya ◽  
KA Orlova ◽  
EA Kolesnikova ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Hpv 16 ◽  
Detection Rates ◽  
High Risk Hpv ◽  
Incident Cases ◽  
Oncogenic Hpv

The purpose of the study was to assess detection rates of human papillomavirus in cervical cancer cases of Nizhny Novgorod. Materials and methods. We used the real-time polymerase chain reaction (PCR) to test samples of mucosa lining of the cervical canal and/or transformation zone taken from 630 women with cervical dysplasia of different degrees and 107 incident cases of cervical cancer that did not undergo treatment. The detection and differentiation of 14 genotypes of high-risk human papillomaviruses (HPV) was carried out using the AmpliSens® HPV HCR-genotype-FRT PRC kit. Results. The overall infection rate of women with oncogenic human papillomaviruses was 41.8%. Among the genotypes, HPV 16 (39.2%), 18 (15.5%), 33 (16.6%), and 56 (11.9%) predominated. A high prevalence of oncogenic HPV was detected in the women with cervical intraepithelial neoplasia (58.1%) and cervical cancer (90%). The spectrum of genotypes in women with neoplasia of various degrees differed. In women with CIN II and CIN III, vaccine-preventable HPV genotypes (HPV 16 and 18) playing the leading role in the development of cervical cancer were the most frequent. The same genotypes dominated in the women with invasive cervical cancer. One oncogenic HPV genotype was usually found in the infected women (69%). The high-risk HPV infection was often combined with Ureaplasma ssp (49.3%), Mycoplasma hominis (20.1%), Cytomegalovirus (21.1%), and Herpes simplex I/II (18.2%) infections. Combinations of high-risk HPV with Chlamydia trachomatis and Herpes 6 were found in 8.3% and 5% of the cases, respectively. Conclusions. Our findings proved a wide prevalence of high carcinogenic risk HPV 16 and 18 genotypes, thus indicating the expediency of using Cervarix and Gardasil vaccines registered in the Russian Federation and containing antigens to these types of virus for specific prevention of the HPV infection.

scholarly journals The Laboratory Diagnosis of Genital Human Papillomavirus Infections

2005 ◽  
Vol 16 (2) ◽  
pp. 83-91 ◽  
Author(s):  
François Coutlee ◽  
Danielle Rouleau ◽  
Alex Ferenczy ◽  
Eduardo Franco
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
High Grade ◽  
Hpv Testing ◽  
Screening Programs ◽  
Detection Techniques ◽  
Hpv Types ◽  
High Risk Hpv

Human papillomaviruses (HPVs) are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA) are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.

scholarly journals Involvement of Nuclear Export in Human Papillomavirus Type 18 E6-Mediated Ubiquitination and Degradation of p53

2005 ◽  
Vol 79 (14) ◽  
pp. 8773-8783 ◽  
Author(s):  
Deborah Stewart ◽  
Anirban Ghosh ◽  
Greg Matlashewski
Keyword(s):  
High Risk ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Cellular Level ◽  
Human Papillomaviruses ◽  
Leptomycin B ◽  
Proteasome Pathway ◽  
High Risk Hpv

ABSTRACT The E6 protein from high-risk human papillomaviruses (HPVs) targets the p53 tumor suppressor for degradation by the proteasome pathway. This ability contributes to the oncogenic potential of these viruses. However, several aspects concerning the mechanism of E6-mediated p53 degradation at the cellular level remain to be clarified. This study therefore examined the role of cell localization and ubiquitination in the E6-mediated degradation of p53. As demonstrated within, following coexpression both p53 and high-risk HPV type 18 (HPV-18) E6 (18E6) shuttle from the nucleus to the cytoplasm. Mutation of the C-terminal nuclear export signal (NES) of p53 or treatment with leptomycin B inhibited the 18E6-mediated nuclear export of p53. Impairment of nuclear export resulted in only a partial reduction in 18E6-mediated degradation, suggesting that both nuclear and cytoplasmic proteasomes can target p53 for degradation. This was also consistent with the observation that 18E6 mediated the accumulation of polyubiquitinated p53 in the nucleus. In comparison, a p53 isoform that localizes predominantly to the cytoplasm was not targeted for degradation by 18E6 in vivo but could be degraded in vitro, arguing that nuclear p53 is the target for E6-mediated degradation. This study supports a model in which (i) E6 mediates the accumulation of polyubiquitinated p53 in the nucleus, (ii) E6 is coexported with p53 from the nucleus to the cytoplasm via a CRM1 nuclear export mechanism involving the C-terminal NES of p53, and (iii) E6-mediated p53 degradation can be mediated by both nuclear and cytoplasmic proteasomes.

scholarly journals Genotype distribution characteristics of high-risk human papillomaviruses in women from Shanghai, China

2015 ◽  
Vol 144 (7) ◽  
pp. 1482-1489 ◽  
Author(s):  
Y. GU ◽  
M. YI ◽  
Y. XU ◽  
H. ZHAO ◽  
F. FU ◽  
...  
Keyword(s):  
High Risk ◽  
Vaccination Strategy ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Low Risk ◽  
Multiple Infection ◽  
Genotype Distribution ◽  
Infection Rates ◽  
Control And Prevention ◽  
High Risk Hpv

SUMMARYHigh-risk human papillomaviruses (HPVs) are highly prevalent worldwide, and HPV genotype distribution varies regionally. Molecular surveys of HPVs are important for effective HPV control and prevention. Fifteen high-risk HPV strains (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) and six low-risk HPV strains (HPV6, 11, 42, 43, 44, CP8304) were detected by cervical cytology from 10 501 subjects. High-risk HPVs, low-risk HPVs, and both high- and low-risk HPVs were detected in 14·5%, 2·8%, and 2·4% of cases, respectively. Of 1782 subjects with high-risk HPV infection, 75·5%, 18·1%, and 6·4% were infected with one, two, and ⩾3 strains of high-risk HPVs, respectively. HPV52, HPV16, and HPV58 were the top three most dominant high-risk HPV genotypes in our population with positivity rates of 23·0%, 17·7% and 16·9%, respectively. Multiple infection was common, with significantly higher co-infection rates of HPV58/HPV33 (12·9%) and HPV58/HPV52 (11·3%). Further data comparisons showed that HPV genotype distribution varied markedly between domestic and international regions. In conclusion, a monolithic vaccination strategy is obviously impractical, and regional HPV surveillance is essential to optimize current HPV control and prevention.

scholarly journals Protamine Sulfate Is a Potent Inhibitor of Human Papillomavirus InfectionIn Vitro and In Vivo

2021 ◽  
Author(s):  
Jesse M. Young ◽  
Amira Zine El Abidine ◽  
Ricardo A. Gómez-Martinez ◽  
Virginie Bondu ◽  
Rosa T. Sterk ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Heparan Sulfate ◽  
Viral Entry ◽  
Close Contact ◽  
Hpv Infection ◽  
Protamine Sulfate ◽  
Vaccine Uptake ◽  
Host Cells ◽  
Viral Attachment

Human papillomavirus (HPV) infections are transmitted through sexual or other close contact and are etiologically associated with epithelial warts, papillomas, and intraepithelial lesions that may progress to cancer. Indeed, 4.8% of the global cancer burden is linked to HPV infection. Highly effective vaccines protect against two to nine of the most medically important HPV genotypes; yet vaccine uptake is inadequate and/or cost prohibitive in many settings. With HPV-related cancer incidence expected to rise over the coming decades, there is a need for effective HPV microbicides. Herein we demonstrate the strong inhibitory activity of the heparin-neutralizing drug protamine sulfate (PS) against HPV infection. Pretreatment of cells with PS greatly reduced infection regardless of HPV genotype or virus source. Vaginal application of PS prevented infection of the murine genital tract by HPV pseudovirions. Time-of-addition assays where PS was added to cells before infection, during infection, or after viral attachment demonstrated strong inhibitory activities on early infection steps. No effect on virus infection was found for cell lines deficient in heparan sulfate expression, suggesting that PS binds to heparan sulfate on the cell surface. Consistent with this, prophylactic PS exposure prevented viral attachment, including under low pH conditions akin to the human vaginal tract. Our findings suggest PS acts dually to prevent HPV infection: prophylactic treatment prevents HPV attachment to host cells and post-attachment administration alters viral entry. Clinical trials are warranted to determine whether protamine-based products are effective as topical microbicides against genital HPVs.

Comparison of Co-Presence of Epstein-Barr Virus and High-Risk Human Papillomaviruses in Colorectal Cancers in the Middle East Region

2020 ◽  
Author(s):  
Karim Nagi ◽  
Ishita Gupta ◽  
Hamda A Al-Thawadi ◽  
Ayesha Jabeen ◽  
Mohammed I. Malk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Epstein Barr Virus ◽  
Human Papillomaviruses ◽  
Colorectal Cancers ◽  
Barr Virus ◽  
Human Carcinomas ◽  
Epstein Barr ◽  
Invasive Carcinomas ◽  
High Risk Hpv

Background: Several studies have shown the presence of onco viral DNA in colorectal tumor tissues. Viral infection by onco-viruses such as Human papillomaviruses (HPVs) and Epstein–Barr virus (EBV) are well-known to be involved in the onset and/or progression of numerous human carcinomas. Methods: We explored the co-presence of high-risk HPVs and EBV in a cohort of colorectal cancer samples from Lebanon (94) and Syria (102) by PCR, immunohistochemistry and tissue microarray. Results: The results of the study point out that 54% of colorectal cancer cases in Syria are positive for high-risk HPVs, while 30% of the cases in Lebanon are positive for these viruses; the most frequent high-risk HPV types in these populations are 16, 18, 31, 33 and 35. Analysis of LMP1 showed similar results in both populations; 36% of Syrian and 31% of Lebanese samples. Additionally, we report that EBV and high-risk HPVs are co-present in these samples. In Syrian samples, EBV and HPVs are co-present in 16% of the population, however, in the Lebanese samples, 20% of the cases are positive for both EBV and HPVs; their co-presence is associated with high/intermediate grade invasive carcinomas. Conclusion: These data suggest that EBV and high-risk HPVs are co-present in human colorectal cancers where they can cooperate in the progression of these cancers. Nevertheless, further studies are needed to elucidate the role of those oncoviruses in the development of human colorectal carcinomas.

Sign in / Sign up

Export Citation Format

Share Document