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Biological Chemistry Jul 2017Animal and human papillomaviruses (HPVs) replicate persistently in specific types of stratified epithelia of their host. After the initial infection, the viral genome... (Review)
Review
Animal and human papillomaviruses (HPVs) replicate persistently in specific types of stratified epithelia of their host. After the initial infection, the viral genome replicates at low levels in the dividing cells of the epithelium, and these cells form a reservoir of infection that can last for decades. When the infected cells differentiate, viral genomes replicate to high levels to form progeny virus that is released from the surface of the epithelium. This complex life cycle requires several different modes of viral DNA replication, but papillomaviruses are masters at hijacking key cellular processes to facilitate their own reproduction.
Topics: Animals; Genome, Viral; Humans; Papillomaviridae; Viral Proteins; Virus Replication
PubMed: 28315855
DOI: 10.1515/hsz-2017-0113 -
Viruses Aug 2021Papillomaviruses (PVs) are well established to cause hyperplastic papillomas (warts) in humans and animals. In addition, due to their ability to alter cell regulation,... (Review)
Review
Papillomaviruses (PVs) are well established to cause hyperplastic papillomas (warts) in humans and animals. In addition, due to their ability to alter cell regulation, PVs are also recognized to cause approximately 5% of human cancers and these viruses have been associated with neoplasia in a number of animal species. In contrast to other domestic species, cats have traditionally been thought to less frequently develop disease due to PV infection. However, in the last 15 years, the number of viruses and the different lesions associated with PVs in cats have greatly expanded. In this review, the PV life cycle and the subsequent immune response is briefly discussed along with methods used to investigate a PV etiology of a lesion. The seven PV types that are currently known to infect cats are reviewed. The lesions that have been associated with PV infections in cats are then discussed and the review finishes with a brief discussion on the use of vaccines to prevent PV-induced disease in domestic cats.
Topics: Animals; Animals, Domestic; Cat Diseases; Cats; Papillomaviridae; Papillomavirus Infections
PubMed: 34452528
DOI: 10.3390/v13081664 -
Annals of Oncology : Official Journal... Oct 2017High-risk human papillomavirus (HPV) is now recognised as the principal cause of the increasing incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) in some... (Review)
Review
High-risk human papillomavirus (HPV) is now recognised as the principal cause of the increasing incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) in some parts of the world. The primary risk factor for developing HPV-related OPSCC is oral HPV-infection and the majority of oral HPV-infections are acquired by oral sex. Progression into an OPSCC includes persistent infection with evasion of immune response in the microenvironment, the activation of viral early genes (E6, E7) in basal epithelial cells, the deregulation of cell cycle and the accumulation of chromosomal instability. Patients affected by HPV-related OPSCC tend to be younger and have better outcomes. This observation has lead current research to evaluate treatment de-escalation options to reduce long-term associated morbidity. Moreover, a different molecular profile for HPV-related OPSCC has been described, opening new options for targeted therapy and immunotherapy approaches. This paper comprehensively reviews our accumulated knowledge regarding the role of HPV in OPSCC spanning from infection to cancer development, including its clinical diagnosis, management and preventive strategies.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck
PubMed: 28633362
DOI: 10.1093/annonc/mdx304 -
Viruses Apr 2022Beta human papillomavirus (beta HPV) infections are common in adults. Certain types of beta HPVs are associated with nonmelanoma skin cancer (NMSC) in immunocompromised... (Review)
Review
Beta human papillomavirus (beta HPV) infections are common in adults. Certain types of beta HPVs are associated with nonmelanoma skin cancer (NMSC) in immunocompromised individuals. However, whether beta HPV infections promote NMSC in the immunocompetent population is unclear. They have been hypothesized to increase genomic instability stemming from ultraviolet light exposure by disrupting DNA damage responses. Implicit in this hypothesis is that the virus encodes one or more proteins that impair DNA repair signaling. Fluorescence-based reporters, next-generation sequencing, and animal models have been used to test this primarily in cells expressing beta HPV E6/E7. Of the two, beta HPV E6 appears to have the greatest ability to increase UV mutagenesis, by attenuating two major double-strand break (DSB) repair pathways, homologous recombination, and non-homologous end-joining. Here, we review this dysregulation of DSB repair and emerging approaches that can be used to further these efforts.
Topics: Alphapapillomavirus; Animals; DNA Repair; Homologous Recombination; Papillomaviridae; Papillomavirus Infections; Skin Neoplasms
PubMed: 35632690
DOI: 10.3390/v14050948 -
Viruses Aug 2017While the majority of Human papillomavirus (HPV) infections are transient and cleared within a couple of years following exposure, 10-20% of infections persist latently,... (Review)
Review
While the majority of Human papillomavirus (HPV) infections are transient and cleared within a couple of years following exposure, 10-20% of infections persist latently, leading to disease progression and, ultimately, various forms of invasive cancer. Despite the clinical efficiency of recently developed multivalent prophylactic HPV vaccines, these preventive measures are not effective against pre-existing infection. Additionally, considering that the burden associated with HPV is greatest in regions with limited access to preventative vaccination, the development of effective therapies targeting persistent infection remains imperative. This review discusses not only the mechanisms underlying persistent HPV infection, but also the promise of immunomodulatory therapeutic vaccines and small-molecular inhibitors, which aim to augment the host immune response against the viral infection as well as obstruct critical viral-host interactions.
Topics: Antiviral Agents; Female; Humans; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines
PubMed: 28820433
DOI: 10.3390/v9080229 -
Virology Oct 2013The papillomavirus E2 proteins are pivotal to the viral life cycle and have well characterized functions in transcriptional regulation, initiation of DNA replication and... (Review)
Review
The papillomavirus E2 proteins are pivotal to the viral life cycle and have well characterized functions in transcriptional regulation, initiation of DNA replication and partitioning the viral genome. The E2 proteins also function in vegetative DNA replication, post-transcriptional processes and possibly packaging. This review describes structural and functional aspects of the E2 proteins and their binding sites on the viral genome. It is intended to be a reference guide to this viral protein.
Topics: Animals; Base Sequence; Binding Sites; DNA-Binding Proteins; Genome, Viral; Mutation; Oncogene Proteins, Viral; Papillomaviridae; Protein Processing, Post-Translational; Protein Stability; Protein Structure, Tertiary; Transcriptional Activation; Virus Assembly; Virus Replication
PubMed: 23849793
DOI: 10.1016/j.virol.2013.06.006 -
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 Clinical Virology : the... Jul 2009
Topics: Female; Humans; Molecular Diagnostic Techniques; Papillomaviridae; Papillomavirus Infections; Virology
PubMed: 19651362
DOI: 10.1016/S1386-6532(09)00331-X -
Viruses May 2022Papillomaviruses (PV) replicate in undifferentiated keratinocytes at low levels and to high levels in differentiated cells. The restricted replication in... (Review)
Review
Papillomaviruses (PV) replicate in undifferentiated keratinocytes at low levels and to high levels in differentiated cells. The restricted replication in undifferentiated cells is mainly due to the expression of the conserved viral E8^E2 repressor protein, a fusion protein consisting of E8 and the hinge, DNA-binding, and dimerization domain of E2. E8^E2 binds to viral genomes and represses viral transcription and genome replication by recruiting cellular NCoR/SMRT-HDAC3 corepressor complexes. Tissue culture experiments have revealed that E8^E2 modulates long-term maintenance of extrachromosomal genomes, productive replication, and immortalization properties in a virus type-dependent manner. Furthermore, in vivo experiments have indicated that Mus musculus PV1 E8^E2 is required for tumor formation in immune-deficient mice. In summary, E8^E2 is a crucial inhibitor whose levels might determine the outcome of PV infections.
Topics: Animals; DNA-Binding Proteins; Mice; Papillomaviridae; Papillomavirus Infections; Viral Proteins; Virus Replication
PubMed: 35632695
DOI: 10.3390/v14050953 -
Virus Research Mar 2017Preclinical model systems to study multiple features of the papillomavirus life cycle have greatly aided our understanding of Human Papillomavirus (HPV) biology, disease... (Review)
Review
Preclinical model systems to study multiple features of the papillomavirus life cycle have greatly aided our understanding of Human Papillomavirus (HPV) biology, disease progression and treatments. The challenge to studying HPV in hosts is that HPV along with most PVs are both species and tissue restricted. Thus, fundamental properties of HPV viral proteins can be assessed in specialized cell culture systems but host responses that involve innate immunity and host restriction factors requires preclinical surrogate models. Fortunately, there are several well-characterized and new animal models of papillomavirus infections that are available to the PV research community. Old models that continue to have value include canine, bovine and rabbit PV models and new rodent models are in place to better assess host-virus interactions. Questions arise as to the strengths and weaknesses of animal PV models for HPV disease and how accurately these preclinical models predict malignant progression, vaccine efficacy and therapeutic control of HPV-associated disease. In this review, we examine current preclinical models and highlight the strengths and weaknesses of the various models as well as provide an update on new opportunities to study the numerous unknowns that persist in the HPV research field.
Topics: Animals; Bovine papillomavirus 1; Cattle; Cottontail rabbit papillomavirus; Disease Models, Animal; Dogs; Female; Humans; Lambdapapillomavirus; Mice; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Primates; Rabbits; Rats; Skin Neoplasms; Uterine Cervical Neoplasms
PubMed: 27956145
DOI: 10.1016/j.virusres.2016.12.004