scholarly journals Papillomaviruses Go Retro

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 267
Author(s):  
Jian Xie ◽  
Pengwei Zhang ◽  
Mac Crite ◽  
Daniel DiMaio
Keyword(s):  
Retrograde Transport ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Cellular Biology ◽  
Genome Replication ◽  
Intracellular Membrane ◽  
Transport Pathway ◽  
Hpv Dna ◽  
Membrane Bound ◽  
Entry Mechanism

Human papillomaviruses are important pathogens responsible for approximately 5% of cancer as well as other important human diseases, but many aspects of the papillomavirus life cycle are poorly understood. To undergo genome replication, HPV DNA must traffic from the cell surface to the nucleus. Recent findings have revolutionized our understanding of HPV entry, showing that it requires numerous cellular proteins and proceeds via a series of intracellular membrane-bound vesicles that comprise the retrograde transport pathway. This paper reviews the evidence supporting this unique entry mechanism with a focus on the crucial step by which the incoming virus particle is transferred from the endosome into the retrograde pathway. This new understanding provides novel insights into basic cellular biology and suggests novel rational approaches to inhibit HPV infection.

scholarly journals γ-Secretase promotes membrane insertion of the human papillomavirus L2 capsid protein during virus infection

2018 ◽  
Vol 217 (10) ◽  
pp. 3545-3559 ◽  
Author(s):  
Takamasa Inoue ◽  
Pengwei Zhang ◽  
Wei Zhang ◽  
Kylia Goodner-Bingham ◽  
Allison Dupzyk ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Retrograde Transport ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Membrane Insertion ◽  
Human Pathogens ◽  
Transport Pathway ◽  
Chaperone Function ◽  
Endosomal Membranes

Despite their importance as human pathogens, entry of human papillomaviruses (HPVs) into cells is poorly understood. The transmembrane protease γ-secretase executes a crucial function during the early stages of HPV infection, but the role of γ-secretase in infection and the identity of its critical substrate are unknown. Here we demonstrate that γ-secretase harbors a previously uncharacterized chaperone function, promoting low pH–dependent insertion of the HPV L2 capsid protein into endosomal membranes. Upon membrane insertion, L2 recruits the cytosolic retromer, which enables the L2 viral genome complex to enter the retrograde transport pathway and traffic to the Golgi en route for infection. Although a small fraction of membrane-inserted L2 is also cleaved by γ-secretase, this proteolytic event appears dispensable for HPV infection. Our findings demonstrate that γ-secretase is endowed with an activity that can promote membrane insertion of L2, thereby targeting the virus to the productive infectious pathway.

scholarly journals Sequential Recruitment of the Endoplasmic Reticulum and Chloroplasts for Plant Potyvirus Replication

2009 ◽  
Vol 84 (2) ◽  
pp. 799-809 ◽  
Author(s):  
Taiyun Wei ◽  
Tyng-Shyan Huang ◽  
Jamie McNeil ◽  
Jean-François Laliberté ◽  
Jian Hong ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Integral Membrane Protein ◽  
Genome Replication ◽  
Transport Pathway ◽  
Er Exit Sites ◽  
Weight Protein ◽  
Infected Cells ◽  
Membrane Bound ◽  
Viral Replicase ◽  
Positive Strand Rna

ABSTRACT The replication of positive-strand RNA viruses occurs in cytoplasmic membrane-bound virus replication complexes (VRCs). Depending on the virus, distinct cellular organelles such as the endoplasmic reticulum (ER), chloroplast, mitochondrion, endosome, and peroxisome are recruited for the formation of VRC-associated membranous structures. Previously, the 6,000-molecular-weight protein (6K) of plant potyviruses was shown to be an integral membrane protein that induces the formation of 6K-containing membranous vesicles at endoplasmic reticulum (ER) exit sites for potyvirus genome replication. Here, we present evidence that the 6K-induced vesicles predominantly target chloroplasts, where they amalgamate and induce chloroplast membrane invaginations. The vesicular transport pathway and actomyosin motility system are involved in the trafficking of the 6K vesicles from the ER to chloroplasts. Viral RNA, double-stranded RNA, and viral replicase components are concentrated at the 6K vesicles that associate with chloroplasts in infected cells, suggesting that these chloroplast-bound 6K vesicles are the site for potyvirus replication. Taken together, these results suggest that plant potyviruses sequentially recruit the ER and chloroplasts for their genome replication.

scholarly journals A high yield gold nanoparticle-based DNA isolation method for human papillomaviruses genotypes from cervical cancer tissue samples

2019 ◽  
Author(s):  
Noorossadat Seyyedi ◽  
Fatemeh Farjadian ◽  
Ali Farhadi ◽  
Gholamreza Rafiei Dehbidi ◽  
Reza Ranjbaran ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dna Sequences ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
High Yield ◽  
Cancer Tissue ◽  
Purification Method ◽  
Tissue Samples ◽  
Hpv Dna ◽  
Cervical Cancer Tissue

Gold nanoparticles (AuNPs) are commonly used in biosensors of various kinds. The purification of DNA from cancer tissues is an important step in diagnostic and therapeutic development, but current methods are not optimal. Many cervical cancer patients are also susceptible to high-risk human papillomavirus (HR-HPV) infection. Accurate viral diagnosis has so far relied on the extraction of adequate amounts of DNA from formalin-fixed, paraffin-embedded (FFPE) tissue samples. Since the sensitivity and specificity of commercially available purification kits are not optimal, we designed a DNA purification method based on AuNPs to purify sufficient amounts of HR-HPV DNA from cervical cancer tissue samples. AuNPs were coated with a series of oligonucleotide probes to hybridize to specific DNA sequences of HR-HPV genotypes. With this method, we recovered 733 out of 800 copies of type-specific HPV DNA with complete specificity, compared to 36 copies with a standard commercial kit (Qiagen FFPE).

scholarly journals The Epidemiology of Human Papillomavirus Infection and Cervical Cancer

2007 ◽  
Vol 23 (4) ◽  
pp. 213-227 ◽  
Author(s):  
F. Xavier Bosch ◽  
Silvia de Sanjosé
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Transmitted Infection ◽  
Hpv Dna ◽  
Sexually Transmitted ◽  
Papillomavirus Infection ◽  
Simplex Virus

Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI). The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs). The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC), the adenocarcinomas and the vast majority (i.e. > 95%) of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL)/Cervical Intraepithelial Neoplasia 3 (CIN3)/Carcinomain situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC) for five or more years, smoking, high parity (five or more full term pregnancies) and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT) and Herpes Simplex Virus type 2 (HSV-2). Women exposed to the Human Immunodeficiency Virus (HIV) are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer.

scholarly journals Cell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry

2020 ◽  
Vol 117 (11) ◽  
pp. 6121-6128 ◽  
Author(s):  
Pengwei Zhang ◽  
Ruben Moreno ◽  
Paul F. Lambert ◽  
Daniel DiMaio
Keyword(s):  
Human Papillomavirus ◽  
Virus Replication ◽  
Protein Interactions ◽  
Retrograde Transport ◽  
Hpv Infection ◽  
Cellular Protein ◽  
Protein Protein Interactions ◽  
Transport Pathway ◽  
Viral Genomes ◽  
Cell Penetrating

Virus replication requires critical interactions between viral proteins and cellular proteins that mediate many aspects of infection, including the transport of viral genomes to the site of replication. In human papillomavirus (HPV) infection, the cellular protein complex known as retromer binds to the L2 capsid protein and sorts incoming virions into the retrograde transport pathway for trafficking to the nucleus. Here, we show that short synthetic peptides containing the HPV16 L2 retromer-binding site and a cell-penetrating sequence enter cells, sequester retromer from the incoming HPV pseudovirus, and inhibit HPV exit from the endosome, resulting in loss of viral components from cells and in a profound, dose-dependent block to infection. The peptide also inhibits cervicovaginal HPV16 pseudovirus infection in a mouse model. These results confirm the retromer-mediated model of retrograde HPV entry and validate intracellular virus trafficking as an antiviral target. More generally, inhibiting virus replication with agents that can enter cells and disrupt essential protein-protein interactions may be applicable in broad outline to many viruses.

scholarly journals High HPV Infection Prevalence in Men from Infertile Couples and Lack of Relationship between Seminal HPV Infection and Sperm Quality

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Barbara Golob ◽  
Mario Poljak ◽  
Ivan Verdenik ◽  
Mojca Kolbezen Simoniti ◽  
Eda Vrtačnik Bokal ◽  
...  
Keyword(s):  
Sperm Quality ◽  
External Genitalia ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Sperm Parameters ◽  
Infection Prevalence ◽  
Hpv Dna ◽  
Abnormal Sperm ◽  
Hpv Types ◽  
Infertile Couples

Human papillomaviruses (HPV) are the most frequently sexually transmitted viruses and etiological agents of several human cancers. Controversial results of the role of HPV in infertile population on sperm parameters have been published. The aim of this study was to estimate the type-specific prevalence of HPV DNA infection of the external genitalia and semen in 340 Slovenian men from infertile couples and to establish the relationship between seminal HPV DNA infection and abnormal sperm parameters. Self-taken swabs of the entire penile surface and semen samples were collected, and HPV detection and genotyping were performed. HPV DNA was detected in 37.12% of external genitalia and in 13.61% of semen samples with high HPV type concordance of both sampling sites. The most prevalent HPV types in the male external genitalia were HPV-CP6108 and HPV-84. The most prevalent HPV types in semen were HPV-53 and HPV-CP6108. The prevalence of HPV infection between normozoospermic men and men with abnormal sperm parameters did not differ significantly. Sperm quality did not differ significantly between men with seminal HPV infection and uninfected men. In conclusion, the men from infertile couples are equally susceptible to HPV infection regardless of their fertile potential; seminal HPV infection does not impair sperm quality.

Head and Neck Squamous Cell Carcinomas Associated with Human Papillomaviruses and an Increased Incidence of Cervical Pathology

1988 ◽  
Vol 99 (3) ◽  
pp. 296-301 ◽  
Author(s):  
Norris K. Lee ◽  
Diane B. Ritter ◽  
Abby E. Gross ◽  
David J. Myssiorek ◽  
Anna S. Kadish ◽  
...  
Keyword(s):  
Head And Neck ◽  
Dna Analysis ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Aerodigestive Tract ◽  
Upper Aerodigestive Tract ◽  
Hpv Dna ◽  
Female Patients ◽  
Papanicolaou Smears ◽  
Dna Types

Human papillomaviruses (HPVs) have been identified in benign and cancerous epithelial lesions of the femal genital tract. They have also been identified in papillomata and cancers of the upper aerodigestive tract. This study investigates the hypothesis that lesions of the cervicovaginal area are more common in women with cancers of the head and neck region. The presence of HPV in lesions of both regions is examined. Seven female patients with cancer of the upper aerodigestive tract had DNA analysis of their carcinoma specimens. HPV type 16 was found in two of the seven (28%). Fourteen female patients with upper aerodigestive tract cancers had Papanicolaou smears to search for cytologic evidence of HPV infection, and cervicovaginal lavages to analyze DNA from exfoliated cervical cells. Five of thirteen (38%) Papanicolaou smears revealed koilocytotic atypia and three of these patients had HPV DNA types 16 or 18 identified in the cervical lavage. The incidence of cervical atypia noted is 13-fold greater than average. One patient had HPV type 16 in both her supraglottic cancer and in her cervicovaginal lavage. Evidence of HPV infection at two separate anatomic sites suggests a systemic susceptibility to HPV infection.

scholarly journals Circulating HPV DNA in the Management of Oropharyngeal and Cervical Cancers: Current Knowledge and Future Perspectives

2021 ◽  
Vol 10 (7) ◽  
pp. 1525
Author(s):  
Eriseld Krasniqi ◽  
Maddalena Barba ◽  
Aldo Venuti ◽  
Laura Pizzuti ◽  
Federico Cappuzzo ◽  
...  
Keyword(s):  
Clinical Management ◽  
Detection Rate ◽  
New Technologies ◽  
Current Knowledge ◽  
Digital Pcr ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Hpv Dna ◽  
Cervical Cancers ◽  
Ct Dna

Human papillomaviruses (HPVs) are associated with invasive malignancies, including almost 100% of cervical cancers (CECs), and 35–70% of oropharyngeal cancers (OPCs). HPV infection leads to clinical implications in related tumors by determining better prognosis and predicting treatment response, especially in OPC. Currently, specific and minimally invasive tests allow for detecting HPV-related cancer at an early phase, informing more appropriately therapeutical decisions, and allowing for timely disease monitoring. A blood-based biomarker detectable in liquid biopsy represents an ideal candidate, and the use of circulating HPV DNA (ct-DNA) itself could offer the highest specificity for such a scope. Circulating HPV DNA is detectable in the greatest part of patients affected by HPV-related cancers, and studies have demonstrated its potential usefulness for CEC and OPC clinical management. Unfortunately, when using conventional polymerase chain reaction (PCR), the detection rate of serum HPV DNA is low. Innovative techniques such as droplet-based digital PCR and next generation sequencing are becoming increasingly available for the purpose of boosting HPV ct-DNA detection rate. We herein review and critically discuss the most recent and representative literature, concerning the role of HPV ctDNA in OPC and CEC in the light of new technologies that could improve the potential of this biomarker in fulfilling many of the unmet needs in the clinical management of OPC and CEC patients.

scholarly journals Variants of human papillomaviruses 16 and 18 and their natural history in human immunodeficiency virus-positive women

2005 ◽  
Vol 86 (10) ◽  
pp. 2709-2720 ◽  
Author(s):  
Nicolas F. Schlecht ◽  
Robert D. Burk ◽  
Joel M. Palefsky ◽  
Howard Minkoff ◽  
Xiaonan Xue ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Pap Smear ◽  
Large Population ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Hpv Dna ◽  
Hiv Positive Women ◽  
Hiv Coinfection ◽  
Immunodeficiency Virus ◽  
Women Of African Descent

Highly oncogenic human papillomavirus (HPV) 16 and 18 variants might be expected to be particularly aggressive in HIV-positive women. The association of HPV16 and 18 variant lineages with race, human immunodeficiency virus (HIV) coinfection, CD4+ T-cell count, HIV-RNA level, time-to-clearance of HPV infection and presence of squamous intraepithelial lesions (SIL) among women in the Women's Interagency HIV Study was studied. Subjects were followed semi-annually with Pap smear and cervicovaginal lavage (CVL). HPV DNA was detected in CVLs using MY09/11 L1 PCR assay. Specimens positive for HPV16/18 underwent E6 PCR and sequencing to determine the variant present. Specimens from 195 HPV16- and 162 HPV18-positive women were classified into variant lineages based on sequencing results. African variants of HPV16 and HPV18 were significantly more prevalent among African-Americans than among Caucasians [42 versus 14 % (P=0·001) and 60 versus 13 % (P<0·001), respectively]. However, it was not possible to detect associations between the HPV16 or 18 variant lineages and other factors studied. African variants of HPV16/18 were more common in women of African descent living outside Africa, which could reflect mixing behaviours and/or immunogenetic factors. However, in a large population of HIV-infected women, the variant of HPV16 or 18 was unrelated to persistence of infection or presence of SIL. If non-European variants are more oncogenic, the effect may involve a late stage in cervical tumorigenesis.

scholarly journals Immunohistochemical Detection of early and late Human Papillomaviruses (HPV) proteins in Retinoblastoma tumor

2020 ◽  
Author(s):  
Nara Diniz Soares Pessoa ◽  
Thatiana Correia Melo ◽  
Rodrigo Pinheiro Araldi ◽  
Rofrigo Franco Carvalho ◽  
Willy Becak ◽  
...  
Keyword(s):  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Immunohistochemical Detection ◽  
Hpv Dna ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Retinoblastoma Tumor ◽  
Formalin Fixed

In this study, we evaluated the presence of early and late Human Papillomavirus (HPV) proteins in retinoblastoma Brazilian patients. For this, 8 formalin-fixed paraffin-embedded retinoblastoma tissue blocks were used. HPV DNA presence was determined by in situ hybridization (ISH). Immunohistochemistry were performed to verify HPV16/18 E6, E1^E4, and L1 proteins. HPV was detected in all retinoblastoma tumors and viral DNA was labeled in tumor cells, retinal layers and optical nerve structures. In addition, E1^E4, E6 and L1 proteins were detected in all samples in the same areas where HPV DNA was detected. Our data showed the presence and expression of early and late HPV proteins in retinoblastoma tumors from Brazilian children. However, further studies should be performed to clarify the role of HPV infection in retinoblastoma tumor.

Sign in / Sign up

Export Citation Format

Share Document