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International Journal of Oncology Sep 2019Human papillomavirus (HPV) is the most common sexually transmitted infection, exhibiting a tropism for the epidermis and mucosae. The link between persistent HPV... (Review)
Review
Human papillomavirus (HPV) is the most common sexually transmitted infection, exhibiting a tropism for the epidermis and mucosae. The link between persistent HPV infection and malignancies involving the anogenital tract as well as the head and neck has been well‑established, and it is estimated that HPV‑related cancers involving various anatomical sites account for 4.5% of all human cancers. Current prophylactic vaccines against HPV have enabled the prevention of associated malignancies. However, the sizeable population base of current infection in whom prophylactic vaccines are not applicable, certain high‑risk HPV types not included in vaccines, and the vast susceptible population in developing countries who do not have access to the costly prophylactic vaccines, put forward an imperative need for effective therapies targeting persistent infection. In this article, the life cycle of HPV, the mechanisms facilitating HPV evasion of recognition and clearance by the host immune system, and the promising therapeutic strategies currently under investigation, particularly antiviral drugs and therapeutic vaccines, are reviewed.
Topics: Antiviral Agents; Humans; Immune Evasion; Life Cycle Stages; Neoplasms; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines
PubMed: 31364734
DOI: 10.3892/ijo.2019.4847 -
Virology Jun 2004One hundred eighteen papillomavirus (PV) types have been completely described, and a yet higher number of presumed new types have been detected by preliminary data such... (Review)
Review
One hundred eighteen papillomavirus (PV) types have been completely described, and a yet higher number of presumed new types have been detected by preliminary data such as subgenomic amplicons. The classification of this diverse group of viruses, which include important human pathogens, has been debated for three decades. This article describes the higher-order PV taxonomy following the general criteria established by the International Committee on the Taxonomy of Viruses (ICTV), reviews the literature of the lower order taxa, lists all known "PV types", and interprets their phylogenetic relationship. PVs are a taxonomic family of their own, Papillomaviridae, unrelated to the polyomaviruses. Higher-order phylogenetic assemblages of PV types, such as the "genital human PVs", are considered a genus, the latter group, for example, the genus "Alpha-Papillomavirus". Lower-order assemblages of PV types within each genus are treated as species because they are phylogenetically closely related, but while they have distinct genomic sequences, they have identical or very similar biological or pathological properties. The taxonomic status of PV types, subtypes, and variants remains unchanged and is based on the traditional criteria that the sequence of their L1 genes should be at least 10%, 2-10%, and maximally 2% dissimilar from one another.
Topics: Papillomaviridae; Phylogeny
PubMed: 15183049
DOI: 10.1016/j.virol.2004.03.033 -
Journal of Virology Apr 2020Animal models of viral pathogenesis are essential tools in human disease research. Human papillomaviruses (HPVs) are a significant public health issue due to their... (Review)
Review
Animal models of viral pathogenesis are essential tools in human disease research. Human papillomaviruses (HPVs) are a significant public health issue due to their widespread sexual transmission and oncogenic potential. Infection-based models of papillomavirus pathogenesis have been complicated by their strict species and tissue specificity. In this Gem, we discuss the discovery of a murine papillomavirus, Mus musculus papillomavirus 1 (MmuPV1), and how its experimental use represents a major advancement in models of papillomavirus-induced pathogenesis/carcinogenesis, and their transmission.
Topics: Animals; Carcinogenesis; Disease Models, Animal; Mice; Papillomaviridae; Papillomavirus Infections
PubMed: 32051276
DOI: 10.1128/JVI.00002-20 -
Virology Jun 2021We assessed the quality of human papillomavirus (HPV) sequences in GenBank by analyzing the possible presence of chimeras, "wrong-assembled" contigs and errors in...
We assessed the quality of human papillomavirus (HPV) sequences in GenBank by analyzing the possible presence of chimeras, "wrong-assembled" contigs and errors in taxonomy using an open-source script (HPVChimera_Gb) that compared 25 638 HPV-related nucleotide sequences in GenBank with the 221 numbered HPV types and another 220 complete HPV sequences. There were 110 sequences with taxonomy/naming errors (sequences reported as another HPV type than the one they corresponded to) and 1318 possibly chimeric sequences. Manual analysis found plausible explanations for most of them (e.g. sequence covering an integration site) but 114 sequences appeared to be chimeras (96/114 were already flagged as "unverified" by GenBank) and 13 had taxonomy/naming errors. When comparing all correct HPV sequences in GenBank, there appeared to exist about 800 unique putative HPV types. Systematic and regular work towards eliminating chimeric sequences and taxonomy/naming errors could increase the quality and order in HPV research.
Topics: Amino Acid Sequence; Base Sequence; Classification; Databases, Nucleic Acid; Humans; Papillomaviridae
PubMed: 33730650
DOI: 10.1016/j.virol.2021.03.002 -
Journal of Virology Oct 2016The human papillomavirus (HPV) life cycle is tightly linked to differentiation of the infected epithelium. This means that viral proteins must exert control over... (Review)
Review
The human papillomavirus (HPV) life cycle is tightly linked to differentiation of the infected epithelium. This means that viral proteins must exert control over epithelial gene expression in order to optimize viral production. The HPV E2 protein controls replication, transcription, and viral genome partitioning during the viral infectious life cycle. It consists of a nucleic acid-binding domain and a protein-protein interaction domain separated by a flexible serine and arginine-rich hinge region. Over the last few years, mounting evidence has uncovered an important new role for E2 in viral and cellular RNA processing. This Gem discusses the role of E2 in controlling the epithelial cellular environment and how E2 might act to coordinate late events in the viral replication cycle.
Topics: Epithelial Cells; Humans; Papillomaviridae; RNA Processing, Post-Transcriptional; Transcription, Genetic; Viral Proteins; Virus Replication
PubMed: 27412596
DOI: 10.1128/JVI.00502-16 -
Archives of Virology Feb 2014For many years, research on bovine papillomavirus (BPV) has contributed to the understanding of papillomavirus-induced pathology in humans and animals. The present... (Review)
Review
For many years, research on bovine papillomavirus (BPV) has contributed to the understanding of papillomavirus-induced pathology in humans and animals. The present review shows how recent studies on BPV keep providing evidence concerning key points in viral infection, such as the expression of viral proteins in lymphocytes and the occurrence of productive infections of the placenta. Studies on BPV-induced tumours also provide important information concerning the mechanisms of oncogenesis and immune evasion, as in the cases of connexin 43 down-regulation with loss of intercellular gap junctions and Toll-like receptor 4 (TLR4) down-regulation in equine sarcoids. The biological functions of viral proteins are also being further clarified, as in the case of E2, which was recently shown to load BPV genomes into host chromosomes during the S phase, a process mediated by the ChlR1 protein. In the near future, the ongoing efforts to characterize and classify additional emerging BPV types are likely to broaden even further the possibilities for research.
Topics: Animals; Cattle; Cattle Diseases; Host-Pathogen Interactions; Papillomaviridae; Papillomavirus Infections
PubMed: 23929231
DOI: 10.1007/s00705-013-1801-9 -
Vaccine Nov 2012Human papillomaviruses (HPVs) comprise a diverse group, and have different epithelial tropisms and life-cycle strategies. Many HPVs are classified as low-risk, as they... (Review)
Review
Human papillomaviruses (HPVs) comprise a diverse group, and have different epithelial tropisms and life-cycle strategies. Many HPVs are classified as low-risk, as they are only very rarely associated with neoplasia or cancer in the general population. These HPVs typically cause inapparent/inconspicuous infections, or benign papillomas, which can persist for months or years, but which are eventually resolved by the host's immune system. Low-risk HPVs are difficult to manage in immunosuppressed people and in individuals with genetic predispositions, and can give rise to papillomatosis, and in rare instances, to cancer. The high-risk HPV types are, by contrast, a cause of several important human cancers, including almost all cases of cervical cancer, a large proportion of other anogenital cancers and a growing number of head and neck tumours. The high-risk HPV types constitute a subset of the genus Alphapapillomavirus that are prevalent in the general population, and in most individuals cause only inconspicuous oral and genital lesions. Cancer progression is associated with persistent high-risk HPV infection and with deregulated viral gene expression, which leads to excessive cell proliferation, deficient DNA repair, and the accumulation of genetic damage in the infected cell. Although their life-cycle organisation is broadly similar to that of the low-risk HPV types, the two groups differ significantly in their capacity to drive cell cycle entry and cell proliferation in the basal/parabasal cell layers. This is thought to be linked, at least in part, to different abilities of the high- and low-risk E6 proteins to modulate the activity of p53 and PDZ-domain proteins, and the differential ability of the E7 proteins to target the several different members of the retinoblastoma protein family. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.
Topics: Host-Pathogen Interactions; Humans; Papillomaviridae; Papillomavirus Infections
PubMed: 23199966
DOI: 10.1016/j.vaccine.2012.06.083 -
Seminars in Cancer Biology Dec 1990Human papillomaviruses (HPVs) appear to play a role in the etiology of the vast majority of virus-associated human malignancies. Studies of viral gene expression in... (Review)
Review
Human papillomaviruses (HPVs) appear to play a role in the etiology of the vast majority of virus-associated human malignancies. Studies of viral gene expression in carcinomas suggest the importance of two HPV encoded proteins, E6 and E7, in malignant development and these proteins have been shown to encode transforming and immortalising activities. The two proteins show some functional resemblance to the transforming proteins of other small DNA tumour viruses such as adenovirus and SV40. Recent evidence suggests that one important function of these virus-encoded proteins is binding the products of the cellular tumour suppressor genes RB and p53, revealing an exciting link between oncogenes and anti-oncogenes.
Topics: Amino Acid Sequence; Female; Humans; Molecular Sequence Data; Oncogene Proteins; Papillomaviridae; Viral Proteins
PubMed: 1966493
DOI: No ID Found -
Disease Markers 2007Human papillomaviruses (HPVs) are a diverse group of viruses that cause epithelial lesions of varying severity. Of the 100 or so types that have been identified, around... (Review)
Review
Human papillomaviruses (HPVs) are a diverse group of viruses that cause epithelial lesions of varying severity. Of the 100 or so types that have been identified, around 40 can infect the cervix, with a subset of these causing lesions that can progress to high-grade neoplasia and cervical cancer. These high-risk types are prevalent in the general population, and can predispose to the development of cancer in women who cannot resolve their infection. Virus infection usually leads to the establishment of productive flat warts, or to maintenance of the viral genome in an asymptomatic or latent state. Virus synthesis depends on the ordered expression of viral gene products as the infected basal cell migrates towards the epithelial surface. E7 is expressed in the lower epithelial layers, and is followed eventually by the expression of E4 and L1 closer to the epithelial surface. This ordered pattern changes in characteristic ways during neoplastic progression and latency, and can be irreversibly fixed following integration of the viral genome into the host cell chromosome. Our understanding of expression patterns and their significance, is beginning to explain the nature of disease progression, and offers a rational basis for the selection of biomarkers that may be used to predict disease status and prognostic outcome.
Topics: Biomarkers; Biomarkers, Tumor; Cell Proliferation; Female; Genome, Viral; Humans; Male; Papillomaviridae; Papillomavirus Infections; Uterine Cervical Neoplasms; Virus Assembly; Uterine Cervical Dysplasia
PubMed: 17627064
DOI: 10.1155/2007/613150 -
Virology Feb 2009Papillomaviruses establish their productive life cycle in stratified epithelium or mucosa, where the undifferentiated proliferating keratinocytes are the initial targets... (Review)
Review
Papillomaviruses establish their productive life cycle in stratified epithelium or mucosa, where the undifferentiated proliferating keratinocytes are the initial targets for the productive viral infection. Papillomaviruses have evolved mechanisms to adapt to the normal cellular growth control pathways and to adjust their DNA replication and maintenance cycle to contend with the cellular differentiation. We provide overview of the papillomavirus DNA replication in the differentiating epithelium and describe the molecular interactions important for viral DNA replication on all steps of the viral life cycle.
Topics: DNA Replication; DNA, Viral; Genome, Viral; Genomic Instability; Papillomaviridae; Papillomavirus Infections; Virus Replication
PubMed: 19141359
DOI: 10.1016/j.virol.2008.11.032