scholarly journals Potential Effects of Human Papillomavirus Type Substitution, Superinfection Exclusion and Latency on the Efficacy of the Current L1 Prophylactic Vaccines

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 22
Author(s):  
Ian N. Hampson ◽  
Anthony W. Oliver ◽  
Lynne Hampson
Keyword(s):  
Life Cycle ◽  
High Risk ◽  
Outcome Data ◽  
Benign Lesions ◽  
Complex Dynamic ◽  
Papilloma Virus ◽  
Superinfection Exclusion ◽  
Different Types ◽  
Hpv Types ◽  
Type Substitution

There are >200 different types of human papilloma virus (HPV) of which >51 infect genital epithelium, with ~14 of these classed as high-risk being more commonly associated with cervical cancer. During development of the disease, high-risk types have an increased tendency to develop a truncated non-replicative life cycle, whereas low-risk, non-cancer-associated HPV types are either asymptomatic or cause benign lesions completing their full replicative life cycle. HPVs can also be present as non-replicative so-called “latent” infections and they can also show superinfection exclusion, where cells with pre-existing infections with one type cannot be infected with a different HPV type. Thus, the HPV repertoire and replication status present in an individual can form a complex dynamic meta-community which changes with respect to both time and exposure to different HPV types. In light of these considerations, it is not clear how current prophylactic HPV vaccines will affect this system and the potential for iatrogenic outcomes is discussed in light of recent outcome data.

scholarly journals Superinfection Exclusion between Two High-Risk Human Papillomavirus Types during a Coinfection

2018 ◽  
Vol 92 (8) ◽  
pp. e01993-17 ◽  
Author(s):  
Jennifer Biryukov ◽  
Craig Meyers
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Life Cycle ◽  
High Risk ◽  
Cell Surface ◽  
Viral Life Cycle ◽  
Minor Capsid Protein ◽  
Superinfection Exclusion ◽  
Hpv Types ◽  
First Time

ABSTRACTSuperinfection exclusion is a common phenomenon whereby a single cell is unable to be infected by two types of the same pathogen. Superinfection exclusion has been described for various viruses, including vaccinia virus, measles virus, hepatitis C virus, influenza A virus, and human immunodeficiency virus. Additionally, the mechanism of exclusion has been observed at various steps of the viral life cycle, including attachment, entry, viral genomic replication, transcription, and exocytosis. Human papillomavirus (HPV) is the causative agent of cervical cancer. Recent epidemiological studies indicate that up to 50% women who are HPV positive (HPV+) are infected with more than one HPV type. However, no mechanism of superinfection exclusion has ever been identified for HPV. Here, we show that superinfection exclusion exists during a HPV coinfection and that it occurs on the cell surface during the attachment/entry phase of the viral life cycle. Additionally, we are able to show that the minor capsid protein L2 plays a role in this exclusion. This study shows, for the first time, that superinfection exclusion occurs during HPV coinfections and describes a potential molecular mechanism through which it occurs.IMPORTANCESuperinfection exclusion is a phenomenon whereby one cell is unable to be infected by multiple related pathogens. This phenomenon has been described for many viruses and has been shown to occur at various points in the viral life cycle. HPV is the causative agent of cervical cancer and is involved in other anogenital and oropharyngeal cancers. Recent epidemiological research has shown that up to 50% of HPV-positive individuals harbor more than one type of HPV. We investigated the interaction between two high-risk HPV types, HPV16 and HPV18, during a coinfection. We present data showing that HPV16 is able to block or exclude HPV18 on the cell surface during a coinfection. This exclusion is due in part to differences in the HPV minor capsid protein L2. This report provides, for the first time, evidence of superinfection exclusion for HPV and leads to a better understanding of the complex interactions between multiple HPV types during coinfections.

scholarly journals Nucleo-cytoplasmic Shuttling of High Risk Human Papillomavirus E2 Proteins Induces Apoptosis

2005 ◽  
Vol 280 (43) ◽  
pp. 36088-36098 ◽  
Author(s):  
Stéphanie Blachon ◽  
Sophie Bellanger ◽  
Caroline Demeret ◽  
Françoise Thierry
Keyword(s):  
High Risk ◽  
Intracellular Localization ◽  
Low Risk ◽  
Benign Lesions ◽  
Genome Integration ◽  
Hpv Types ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis ◽  
High Risk Hpv ◽  
Transcription And Replication

Human Papillomavirus (HPV) E2 proteins are the major viral regulators of transcription and replication during the viral life cycle. In addition to these conserved functions, we show that E2 proteins from high risk HPV types 16 and 18, which are associated with cervical cancer, can induce apoptosis. In contrast, E2 proteins from low risk HPV types 6 and 11, which are associated with benign lesions, do not cause cell death. We show that the ability to induce apoptosis is linked to the intracellular localization of the respective E2 proteins rather than to inherent properties of the proteins. Although low risk HPV E2 proteins remain strictly nuclear, high risk HPV E2 proteins are present in both the nucleus and the cytoplasm of expressing cells due to exportin-1 receptor (CRM1)-dependent nucleo-cytoplasmic shuttling. Induction of apoptosis is caused by accumulation of E2 in the cytoplasm and involves caspase 8 activation. We speculate that disruption of the E2 gene during viral genome integration in cervical carcinoma provides a means to avoid E2-induced apoptosis and allow initiation of carcinogenesis.

scholarly journals Cellular Changes Induced by Low-Risk Human Papillomavirus Type 11 in Keratinocytes That Stably Maintain Viral Episomes

2001 ◽  
Vol 75 (16) ◽  
pp. 7564-7571 ◽  
Author(s):  
Jennifer T. Thomas ◽  
Stephen T. Oh ◽  
Scott S. Terhune ◽  
Laimonis A. Laimins
Keyword(s):  
Human Papillomavirus ◽  
Life Cycle ◽  
High Risk ◽  
Life Cycles ◽  
Low Risk ◽  
Global Changes ◽  
Culture Methods ◽  
Transfected Cells ◽  
Hpv Types ◽  
High Risk Hpv

ABSTRACT Infections by low-risk papillomavirus types, such as human papillomavirus (HPV) type 6 (HPV-6) and HPV-11, induce benign genital warts that rarely progress to malignancy. In contrast, lesions induced by high-risk HPV types have the potential to progress to cancer. Considerable information is available concerning the pathogenesis of high-risk HPV types, but little is known about the life cycle of low-risk HPV types. Although functionally distinct, both high- and low-risk virus types infect keratinocytes and induce virion production upon differentiation. This information suggests that they may share common mechanisms for regulating their productive life cycles. Using tissue culture methods developed to study high-risk HPV types, we examined the ability of HPV-11 to be stably maintained as episomes following transfection of normal human keratinocytes with cloned viral DNA. HPV-11 genomes were found to be maintained in keratinocytes for extended passages in cultures in 14 independent experiments involving transfection of cloned HPV-11 DNA. Interestingly, the HPV-11-positive cells exhibited an extended life span that averaged approximately twofold longer than that of control neomycin-transfected cells. In organotypic cultures, HPV-11-positive cells exhibited altered differentiation patterns, but the extent of disruption was less severe than that seen with high-risk HPV types. In addition, the amplification of HPV-11 DNA, as well as the induction of several viral messages, was observed following differentiation of transfected cells in semisolid media. To determine whether global changes in cellular gene expression induced by HPV-11 were similar to those observed with high-risk HPV-31 (Y. E. Chang and L. A. Laimins, J. Virol. 74:4174–4182, 2000), microarray analysis of 7,075 expressed sequences was performed. A spectrum of cellular genes different from that previously reported for HPV-31 was found to be activated or repressed by HPV-11. The expression of only a small set of genes was similarly altered by both high- and low-risk HPV types. This result suggests that different classes of HPVs have distinct effects on global cellular transcription patterns during infection. The methods described allow for a genetic analysis of HPV-11 in the context of its differentiation-dependent life cycle.

scholarly journals Cyclic AMP-dependent protein kinase exhibits antagonistic effects on the replication efficiency of different HPV types

2021 ◽  
Author(s):  
Elina Lototskaja ◽  
Olga Sahharov ◽  
Marko Piirsoo ◽  
Martin Kala ◽  
Mart Ustav ◽  
...  
Keyword(s):  
Life Cycle ◽  
High Risk ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Human Papillomaviruses ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Hpv Types ◽  
Kinase A

Several types of widespread human papillomaviruses (HPVs) may induce transformation of infected cells, provoking the development of neoplasms. Two main genera of HPVs are classified as mucosatropic α and cutaneotropic β HPVs, and they both include high-risk cancer-associated species. The absence of antiviral drugs has driven investigations into the details of the molecular mechanisms of the HPV life cycle. HPV replication depends on viral helicase E1 and transcription factor E2. Their biological activities are controlled by numerous cellular proteins, including protein kinases. Here, we report that ubiquitously expressed cyclic AMP-dependent protein kinase A (PKA) differentially regulates the replication of α HPV11, α HPV18 and β HPV5. PKA stimulates the replication of both α HPVs studied but has a more profound effect on the replication of high-risk α HPV18. However, replication of β HPV5 is inhibited by activated PKA in human primary keratinocytes and U2OS cells. We show that activation of PKA signaling by different pharmacological agents induces rapid proteasomal degradation of the HPV5 E2 protein, which in turn leads to the downregulation of E2-dependent transcription. In contrast, PKA-stimulated induction of HPV18 replication is the result of the downregulation of the E8^E2 transcript coding a potent viral transcriptional inhibitor together with rapid upregulation of E1 and E2 protein levels. IMPORTANCE Several types of human papillomaviruses (HPVs) are causative agents of various types of epithelial cancers. Here, we report that ubiquitously expressed cyclic AMP-dependent protein kinase A (PKA) differentially regulates the replication of various types of HPVs during the initial amplification and maintenance phases of the viral life cycle. Replication of the skin cancer-related pathogen HPV5 is suppressed, whereas replication of the cervical cancer-associated HPV18 is activated in response to elevated PKA activity. To inhibit HPV5 replication, PKA targets the viral transcriptional activator E2, inducing its rapid proteasomal degradation. PKA-dependent stimulation of HPV18 replication relies on the downregulation of another E2 gene product, E8^E2, which encodes a potent transcriptional repressor. Our findings highlight, for the first time, protein kinase-related mechanistic differences in the regulation of the replication of mucosal and cutaneous HPV types.

scholarly journals Results of the first human papilloma virus center in Hungary (2007–2011)

2011 ◽  
Vol 152 (45) ◽  
pp. 1804-1807
Author(s):  
Ádám Galamb ◽  
Attila Pajor ◽  
Zoltán Langmár ◽  
Gábor Sobel
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Human Papilloma Virus ◽  
Hpv Testing ◽  
Papilloma Virus ◽  
Cytological Atypia ◽  
Hpv Dna ◽  
International Data ◽  
Hpv Types ◽  
High Risk Hpv

Human papilloma virus (HPV) is the most common sexually transmitted infection in the 21st century. It has been established that infections with specific HPV types are contributing factors to cervical cancer. Approximately 99.7% of cervical cancers are associated with high risk HPV types. HPV testing plays an important role in the prevention, by decreasing the prevalence and the mortality of cervical cancer. There are 16 HPV-centers operating in Hungary, in which patients undergo HPV screening, cervical exams, and treatment based on standardized guidelines. Patients and methods: The first HPV-center was founded in 2007 in Budapest, at the 2nd Department of Obstetrics and Gynecology, Semmelweis University. This study aimed to define the presence and prevalence of HPV-DNA in the cervical swab samples obtained from patients in our center. Authors conducted to assess the age-specific-prevalence, and HPV type distribution, the associated cervical abnormalities, comparing our results with international data. Results: Overall 1155 woman underwent HPV-testing and genotyping, using polymerase chain reaction. Overall, 55.5% of patients had positive test for HPV DNA types, in which 38.5% for high-risk HPV DNA. Overall prevalence was the highest among females aged 15 to 25years (62.9%). The most common HPV type found was the high risk type 16 (19.5% among the patients with positive HPV testing). Presence of high risk HPV with concurrent cervical cytological abnormality was in 32%. More than two-thirds of woman with cytological atypia (70.6%) were infected with two or more high risk HPV types. HPV 16 was detected in 32% of patients with cytological abnormalities. Conclusions: The results suggest that the prevalence of HPV in this study population exceeds the international data. The results attracts the attention the peak prevalence of the high risk types in the youngest age-group, and the higher risk of cervical abnormality in case of presence of two or more HPV types. The dominance of type 16 and 18 was predictable, but the strong attendance of type 51 and 31 among patients who had cytological atypia, was slightly surprising. Orv. Hetil., 2011, 152, 1804–1807.

scholarly journals Detection and Typing of Human Papilloma Virus by Multiplex PCR with Type-Specific Primers

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Francisco Romero-Pastrana
Keyword(s):  
High Risk ◽  
Human Papilloma Virus ◽  
Multiplex Pcr ◽  
Agarose Gel Electrophoresis ◽  
Specific Primers ◽  
Papilloma Virus ◽  
Hpv Typing ◽  
Attractive Option ◽  
Hpv Types ◽  
High Risk Hpv

The primary underlying cause of cervical cancer is infection with one or more high-risk (HR) types of the human papilloma virus (HPV). Detection and typing of HPV have been commonly carried out by PCR-based assays, where HPV detection and typing are two separate procedures. Here, we present a multiplex PCR-based HPV typing assay that detects 20 HPV types (15 HR, 3 probably HR and 2 low risk) using type-specific primers and agarose gel electrophoresis. 46 cervical, urethral, and biopsy samples were analyzed by both Multiplex PCR and PGMY09/11 consensus PCR, and results were compared. 611 samples were further analyzed by Multiplex PCR, 282 were positive for HR HPV, and 101 showed multiple HR HPV infections. The relatively ease and economic accessibility of the method and its improved ability to detect high-risk HPV types in multiple HPV-infected samples make it an attractive option for HPV testing.

scholarly journals Genotyping of High-risk Human Papilloma virus (HPV) among Iraqi women in Baghdad by Multiplex PCR

2015 ◽  
Vol 9 (1) ◽  
pp. 38-45
Author(s):  
Ashna J. Faik Faik ◽  
Mudhafar Q. Saber Saber ◽  
Wisam J. Mohammed Mohammed ◽  
Bashar Z. Ibraheem Ibraheem ◽  
Kawther R. Lateef Lateef ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Human Papilloma Virus ◽  
Multiplex Pcr ◽  
Dna Amplification ◽  
Hpv Infection ◽  
Abnormal Cytology ◽  
Normal Cytology ◽  
Papilloma Virus ◽  
Hpv Types

Human papilloma virus (HPV) infection is a causative factor for cervical cancer. Early detectionrisk HPV types might help to identify women at high risk of cervical cancer. The aim of of highHPV infection in population of rgir hgih determine the occurrence of the present study was toIraqi women in Baghdad by using Multiplex PCR determine the percentage and genotyping ofHuman Papilloma Virus and to put the best prevention and control program in Iraqi women.Study started at January 2009 to March 2010, cervical samples were collected from 856 womenaged 16–70. HPV DNA amplification was performed using HPV High Risk Typing PCR Kit testfor qualitative detection and genotyping of HPV types 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, 66 inHPV was detected in 106 ( 12,38% ) of the study population, with a range of the cervical swabs.16-70 years age groups. Results showed that the overall HPV prevalence twelve genotypes wereidentified, including HPV-33 (18.60%), HPV-35 (18.60%), HPV-56 (18.60%) ,HPV-39(10.85%),HPV-52 (10.08%), HPV-18 (7.75%), HPV-16 (4.65%), HPV-59 (4.65%), HPV-58(2.32%), HPV-31(1.55%), HPV-45(1.55% ) and HPV-66( 0.77%). Of 856, 218 women was also tested by pap smearith normal cytology was 198 ( 90.83%), 24(12.12%) of them were HPV positive, those with w,abnormal cytology was 20 (9.17 %), 5( 25%)of them was HPV positive. In this study unlike otherepidemiological studies, HPV33,35,56 was the most frequent type (55.8%) in Baghdad, followedby HPV39, HPV52, HPV18, HPV16.

Antecedents of parental psychological control: A narrative review grounded in Self-Determination Theory perspective

2020 ◽  
pp. 29-54
Author(s):  
Sebastiano Costa ◽  
Francesca Liga ◽  
Maria Cristina Gugliandolo ◽  
Simona Sireno ◽  
Rosalba Larcan ◽  
...  
Keyword(s):  
Life Cycle ◽  
Social Environment ◽  
Psychological Control ◽  
Self Determination Theory ◽  
Theoretical Framework ◽  
Self Determination ◽  
Parental Psychological Control ◽  
Parental Characteristics ◽  
Different Types ◽  
Control Construct

Self-determination theory has become a consolidated theoretical framework to deepen the psychological control construct. Numerous studies have widely investigated the consequences of the use of this parenting strategy during the life cycle. Although studies focused on the antecedents of parental psychological control are not so numerous, they provide an interesting picture that needs to be systematized and organized. For this reason, this narra-tive review was aimed at describing the studies on the antecedents of psychological control that used SDT as a theoretical framework. These studies were structured according to three categories: Parental Characteristics (or pressure from within), Child Characteristics (pres-sure from below), and Family Social Environment Characteristics (pressure from above). The results highlighted a wealth of studies in each category and indicating the need to con-tinue this line of studies in the future through the integration of the different types of ante-cedents too.

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