scholarly journals Spatial and Functional Organization of Human Papillomavirus Replication Foci in the Productive Stage of Infection

mBio ◽  
2021 ◽  
Author(s):  
Simran Khurana ◽  
Tovah E. Markowitz ◽  
Juraj Kabat ◽  
Alison A. McBride
Keyword(s):  
Human Papillomavirus ◽  
Persistent Infection ◽  
Chronic Infection ◽  
Functional Organization ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Dna Viruses ◽  
Mucosal Epithelium ◽  
Human Cancers ◽  
Replication Foci

Human papillomaviruses are small DNA viruses that cause chronic infection of cutaneous and mucosal epithelium. In some cases, persistent infection with HPV can result in cancer, and 5% of human cancers are the result of HPV infection.

scholarly journals Zombies in TCGA

2015 ◽  
Vol 89 (8) ◽  
pp. 4044-4046 ◽  
Author(s):  
Daniel DiMaio
Keyword(s):  
Human Papillomavirus ◽  
Next Generation Sequencing ◽  
Hela Cells ◽  
Somatic Mutations ◽  
Hpv Infection ◽  
Next Generation ◽  
Human Cancers ◽  
Human Papillomavirus 18 ◽  
Tumor Types ◽  
Generation Sequencing

Next-generation sequencing results obtained to detect somatic mutations in human cancers can also be searched for viruses that contribute to cancer. Recently, human papillomavirus 18 RNA was detected in tumor types not typically associated with HPV infection. Analyses reported in this issue ofJournal of Virologydemonstrate that the apparent presence of HPV18 RNA in these atypical tumors is due in at least some cases to contamination of samples with HeLa cells, which harbor HPV18.

scholarly journals Human Papillomavirus and Cancers

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3772
Author(s):  
Maria Lina Tornesello ◽  
Franco M. Buonaguro
Keyword(s):  
Human Papillomavirus ◽  
Head And Neck ◽  
Persistent Infection ◽  
Significant Proportion ◽  
Neck Region ◽  
Human Papillomaviruses ◽  
Head And Neck Region ◽  
Cervical Cancers ◽  
Squamous Epithelia

Persistent infection with oncogenic human papillomaviruses (HPVs) is the main cause of nearly all cervical cancers as well as of a significant proportion of other malignancies arising from the mucosal squamous epithelia of the anogenital tract as well as of the head and neck region [1]. [...]

scholarly journals Vesicular trafficking permits evasion of cGAS/STING surveillance during initial human papillomavirus infection

2020 ◽  
Vol 16 (11) ◽  
pp. e1009028
Author(s):  
Brittany L. Uhlorn ◽  
Robert Jackson ◽  
Shuaizhi Li ◽  
Shauna M. Bratton ◽  
Koenraad Van Doorslaer ◽  
...  
Keyword(s):  
Viral Entry ◽  
Hpv Infection ◽  
Vesicular Trafficking ◽  
Cationic Lipids ◽  
Human Papillomaviruses ◽  
Cell Nuclei ◽  
Dna Viruses ◽  
Papillomavirus Infection ◽  
Defective Mutant ◽  
Microbial Infections

Oncogenic human papillomaviruses (HPVs) replicate in differentiating epithelium, causing 5% of cancers worldwide. Like most other DNA viruses, HPV infection initiates after trafficking viral genome (vDNA) to host cell nuclei. Cells possess innate surveillance pathways to detect microbial components or physiological stresses often associated with microbial infections. One of these pathways, cGAS/STING, induces IRF3-dependent antiviral interferon (IFN) responses upon detection of cytosolic DNA. Virion-associated vDNA can activate cGAS/STING during initial viral entry and uncoating/trafficking, and thus cGAS/STING is an obstacle to many DNA viruses. HPV has a unique vesicular trafficking pathway compared to many other DNA viruses. As the capsid uncoats within acidic endosomal compartments, minor capsid protein L2 protrudes across vesicular membranes to facilitate transport of vDNA to the Golgi. L2/vDNA resides within the Golgi lumen until G2/M, whereupon vesicular L2/vDNA traffics along spindle microtubules, tethering to chromosomes to access daughter cell nuclei. L2/vDNA-containing vesicles likely remain intact until G1, following nuclear envelope reformation. We hypothesize that this unique vesicular trafficking protects HPV from cGAS/STING surveillance. Here, we investigate cGAS/STING responses to HPV infection. DNA transfection resulted in acute cGAS/STING activation and downstream IFN responses. In contrast, HPV infection elicited minimal cGAS/STING and IFN responses. To determine the role of vesicular trafficking in cGAS/STING evasion, we forced premature viral penetration of vesicular membranes with membrane-perturbing cationic lipids. Such treatment renders a non-infectious trafficking-defective mutant HPV infectious, yet susceptible to cGAS/STING detection. Overall, HPV evades cGAS/STING by its unique subcellular trafficking, a property that may contribute to establishment of infection.

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.

Human Papillomavirus Induced Cervical and Oropharyngeal Cancers: From Mechanisms to Potential Immuno-therapeutic Strategies

2020 ◽  
Vol 21 (3) ◽  
pp. 167-177 ◽  
Author(s):  
Mohd. Saeed ◽  
Syed Mohd Faisal ◽  
Firoz Akhtar ◽  
Saheem Ahmad ◽  
Mousa M. Alreshidi ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Neck Cancer ◽  
Persistent Infection ◽  
Treatment Strategies ◽  
Therapeutic Strategies ◽  
Human Papillomaviruses ◽  
Treatment Results ◽  
Common Cancer ◽  
Hpv Types ◽  
Almost All

The human papillomavirus (HPV) associated infections are the hallmark of cervical and neck cancer. Almost all the cases of cervical cancer (CC) and 70% of oropharyngeal cancer (OC) are, more or less, caused by the persistent infection of HPV. CC is the fourth most common cancer globally, and is commenced by the persistent infection with human papillomaviruses (HPVs), predominantly HPV types; 16 and 18. In the light of the above facts, there is an immediate requirement to develop novel preventive and innovative therapeutic strategies that may help in lower occurrences of HPV mediated cancers. Currently, only radiation and chemical-based therapies are the treatment for HPV mediated neck cancer (NC) and CC. Recent advances in the field of immunotherapy are underway, which are expected to unravel the optimal treatment strategies for the growing HPV mediated cancers. In this review, we decipher the mechanism of pathogenesis with current immunotherapeutic advances in regressing the NC and CC, with an emphasis on immune-therapeutic strategies being tested in clinical trials and predominantly focus on defining the efficacy and limitations. Taken together, these immunological advances have enhanced the effectiveness of immunotherapy and promises better treatment results in coming future.

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 The Cytoskeletal Adaptor Obscurin-Like 1 Interacts with the Human Papillomavirus 16 (HPV16) Capsid Protein L2 and Is Required for HPV16 Endocytosis

2016 ◽  
Vol 90 (23) ◽  
pp. 10629-10641 ◽  
Author(s):  
Elena Wüstenhagen ◽  
Laura Hampe ◽  
Fatima Boukhallouk ◽  
Marc A. Schneider ◽  
Gilles A. Spoden ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Capsid Protein ◽  
Viral Entry ◽  
Adaptor Protein ◽  
Hpv Infection ◽  
Host Factor ◽  
Human Papillomaviruses ◽  
Endocytic Pathway ◽  
Target Cells ◽  
Gene Transduction

ABSTRACTThe human papillomavirus (HPV) capsid protein L2 is essential for viral entry. To gain a deeper understanding of the role of L2, we searched for novel cellular L2-interacting proteins. A yeast two-hybrid analysis uncovered the actin-depolymerizing factor gelsolin, the membrane glycoprotein dysadherin, the centrosomal protein 68 (Cep68), and the cytoskeletal adaptor protein obscurin-like 1 protein (OBSL1) as putative L2 binding molecules. Pseudovirus (PsV) infection assays identified OBSL1 as a host factor required for gene transduction by three oncogenic human papillomavirus types, HPV16, HPV18, and HPV31. In addition, we detected OBSL1 expression in cervical tissue sections and noted the involvement of OBSL1 during gene transduction of primary keratinocytes by HPV16 PsV. Complex formation of HPV16 L2 with OBSL1 was demonstrated in coimmunofluorescence and coimmunoprecipitation studies after overexpression of L2 or after PsV exposure. We observed a strong colocalization of OBSL1 with HPV16 PsV and tetraspanin CD151 at the plasma membrane, suggesting a role for OBSL1 in viral endocytosis. Indeed, viral entry assays exhibited a reduction of viral endocytosis in OBSL1-depleted cells. Our results suggest OBSL1 as a novel L2-interacting protein and endocytosis factor in HPV infection.IMPORTANCEHuman papillomaviruses infect mucosal and cutaneous epithelia, and the high-risk HPV types account for 5% of cancer cases worldwide. As recently discovered, HPV entry occurs by a clathrin-, caveolin-, and dynamin-independent endocytosis via tetraspanin-enriched microdomains. At present, the cellular proteins involved in the underlying mechanism of this type of endocytosis are under investigation. In this study, the cytoskeletal adaptor OBSL1 was discovered as a previously unrecognized interaction partner of the minor capsid protein L2 and was identified as a proviral host factor required for HPV16 endocytosis into target cells. The findings of this study advance the understanding of a so far less well-characterized endocytic pathway that is used by oncogenic HPV subtypes.

scholarly journals Human Papillomavirus Genotype 31 Does Not Express Detectable MicroRNA Levels during Latent or Productive Virus Replication

2006 ◽  
Vol 80 (21) ◽  
pp. 10890-10893 ◽  
Author(s):  
Xuezhong Cai ◽  
Gu Li ◽  
Laimonis A. Laimins ◽  
Bryan R. Cullen
Keyword(s):  
Human Papillomavirus ◽  
Viral Replication ◽  
Virus Replication ◽  
Human Cells ◽  
Human Papillomaviruses ◽  
Replication Cycle ◽  
Dna Viruses ◽  
Infected Cells ◽  
Productive Virus

ABSTRACT It has recently become clear that several pathogenic DNA viruses express virally encoded microRNAs in infected cells. In particular, numerous microRNAs have been identified in a range of human and animal herpesviruses, and individual microRNAs have also been identified in members of the polyoma- and adenovirus families. Although their functions remain largely unknown, it seems likely that these viral microRNAs play an important role in viral replication in vivo. Here we present an analysis of the microRNAs expressed in human cells during the latent and productive phases of the human papillomavirus genotype 31 (HPV31) replication cycle. Although over 500 cellular microRNAs were cloned and identified, not a single HPV31-specific microRNA was obtained. We therefore concluded that HPV31, and possibly human papillomaviruses in general, does not express viral microRNAs.

scholarly journals Current Updates on Cancer-Causing Types of Human Papillomaviruses (HPVs) in East, Southeast, and South Asia

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2691
Author(s):  
Chichao Xia ◽  
Sile Li ◽  
Teng Long ◽  
Zigui Chen ◽  
Paul K. S. Chan ◽  
...  
Keyword(s):  
South Asia ◽  
Head And Neck ◽  
Age Groups ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Diagnostic Methods ◽  
Dna Viruses ◽  
Treatment Regimens ◽  
Hpv Genotypes ◽  
Insight Into

Human papillomavirus (HPV) infection remains one of the most prominent cancer-causing DNA viruses, contributing to approximately 5% of human cancers. While association between HPV and cervical cancers has been well-established, evidence on the attribution of head and neck cancers (HNC) to HPV have been increasing in recent years. Among the cancer-causing HPV genotypes, HPV16 and 18 remain the major contributors to cancers across the globe. Nonetheless, the distribution of HPV genotypes in ethnically, geographically, and socio-economically diverse East, Southeast, and South Asia may differ from other parts of the world. In this review, we garner and provide updated insight into various aspects of HPV reported in recent years (2015–2021) in these regions. We included: (i) the HPV genotypes detected in normal cancers of the uterine cervix and head and neck, as well as the distribution of the HPV genotypes by geography and age groups; (ii) the laboratory diagnostic methods and treatment regimens used within these regions; and (iii) the oncogenic properties of HPV prototypes and their variants contributing to carcinogenesis. More importantly, we also unveil the similarities and discrepancies between these aspects, the areas lacking study, and the challenges faced in HPV studies.

scholarly journals Detection of Human Papillomavirus Type 16 DNA in Consecutive Genital Samples Does Not Always Represent Persistent Infection as Determined by Molecular Variant Analysis

2000 ◽  
Vol 38 (9) ◽  
pp. 3388-3393 ◽  
Author(s):  
Marie-Hélène Mayrand ◽  
François Coutlée ◽  
Catherine Hankins ◽  
Normand Lapointe ◽  
Pierre Forest ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Persistent Infection ◽  
Single Strand Conformation Polymorphism ◽  
Hpv Infection ◽  
Sscp Analysis ◽  
Long Control Region ◽  
Hpv 16 ◽  
Additional Information ◽  
Molecular Variant ◽  
Variant Analysis

Persistent human papillomavirus (HPV) infection of the uterine cervix is a risk factor for progression to high-grade squamous intraepithelial lesions. Detection in consecutive genital samples of HPV-16 DNA, a frequently encountered HPV type, may represent persistent infection or reinfection. We undertook a study using PCR–single-strand conformation polymorphism (SSCP) analysis and sequencing of PCR products (PCR-sequencing) to determine if consecutive HPV-16-positive samples contained the same HPV-16 variant. Fifty women (36 human immunodeficiency virus [HIV] seropositive, 14 HIV seronegative) had at least two consecutive genital specimens obtained at 6-month intervals that contained HPV-16 DNA as determined by a consensus L1 PCR assay. A total of 144 samples were amplified with two primer pairs for SSCP analysis of the entire long control region. Fifteen different SSCP patterns were identified in our population, while 22 variants were identified by PCR-sequencing. The most frequent SSCP pattern was found in 75 (53%) samples from 27 (54%) women. The SSCP patterns obtained from consecutive specimens were identical for 46 (92%) of 50 women, suggesting persistent infection. Four women exhibited in consecutive specimens different HPV-16 SSCP patterns that were all confirmed by PCR-sequencing. The additional information on the nature of persistent infection provided by molecular variant analysis was useful for 6% of women, since three of the four women who did not have identical consecutive specimens would have been misclassified as having persistent HPV-16 infection on the basis of HPV typing.

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