scholarly journals Regulation of the Human Papillomavirus Lifecyle through Post-Translational Modifications of the Viral E2 Protein

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 793
Author(s):  
Leny Jose ◽  
Timra Gilson ◽  
Elliot J. Androphy ◽  
Marsha DeSmet
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Viral Replication ◽  
Post Translational Modifications ◽  
E2 Protein ◽  
Tumor Virus ◽  
Viral Lifecycle

The human papillomavirus (HPV) is a DNA tumor virus that infects cutaneous and mucosal epithelia where high-risk (HR) HPV infections lead to cervical, oropharyngeal, and anogenital cancers. Worldwide, nearly 5% of all cancers are caused by HR HPV. The viral E2 protein is essential for episomal replication throughout the viral lifecycle. The E2 protein is regulated by phosphorylation, acetylation, sumoylation, and ubiquitination. In this mini-review, we summarize the recent advancements made to identify post translational modifications within E2 and their ability to control viral replication.

scholarly journals The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 786
Author(s):  
Ryan T. Gibson ◽  
Elliot J. Androphy
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Viral Replication ◽  
Chromatin Immunoprecipitation ◽  
Binding Sites ◽  
Viral Infections ◽  
Hpv Infection ◽  
Regulatory Proteins ◽  
Transactivation Domain ◽  
Structural Maintenance Of Chromosomes

The multi-subunit structural maintenance of chromosomes (SMC) 5/6 complex includes SMC6 and non-SMC element (NSE)3. SMC5/6 is essential for homologous recombination DNA repair and functions as an antiviral factor during hepatitis B (HBV) and herpes simplex-1 (HSV-1) viral infections. Intriguingly, SMC5/6 has been found to associate with high-risk human papillomavirus (HPV) E2 regulatory proteins, but the functions of this interaction and its role during HPV infection remain unclear. Here, we further characterize SMC5/6 interactions with HPV-31 E2 and its role in the HPV life cycle. Co-immunoprecipitation (co-IP) revealed that SMC6 interactions with HPV-31 E2 require the E2 transactivation domain, implying that SMC5/6 interacts with full-length E2. Using chromatin immunoprecipitation, we found that SMC6 is present on HPV-31 episomes at E2 binding sites. The depletion of SMC6 and NSE3 increased viral replication and transcription in keratinocytes maintaining episomal HPV-31, indicating that SMC5/6 restricts the viral replicative program. SMC6 interactions with E2 were reduced in the presence of HPV-31 E1, suggesting that SMC6 and E1 compete for E2 binding. Our findings demonstrate SMC5/6 functions as a repressor of the viral replicative program and this may involve inhibiting the initiation of viral replication.

scholarly journals Genetic Analysis of High-Risk E6 in Episomal Maintenance of Human Papillomavirus Genomes in Primary Human Keratinocytes

2002 ◽  
Vol 76 (22) ◽  
pp. 11359-11364 ◽  
Author(s):  
Regina B. Park ◽  
Elliot J. Androphy
Keyword(s):  
Human Papillomavirus ◽  
Dna Replication ◽  
High Risk ◽  
Viral Replication ◽  
Human Keratinocytes ◽  
Binding Motif ◽  
Primary Human Keratinocytes ◽  
Hpv16 E6 ◽  
E6 And E7 ◽  
Episomal Maintenance

ABSTRACT Papillomaviruses possess small DNA genomes that encode five early (E) proteins. Transient DNA replication requires activities of the E1 and E2 proteins and a DNA segment containing their binding sites. The E6 and E7 proteins of cancer-associated human papillomavirus (HPV) transform cells in culture. Recent reports have shown that E6 and E7 are necessary for episomal maintenance of HPV in primary keratinocytes. The functions of E6 necessary for viral replication have not been determined, and to address this question we used a recently developed transfection system based on HPV31. To utilize a series of HPV16 E6 mutations, HPV31 E6 was replaced by its HPV16 counterpart. This chimeric genome was competent for both transient and stable replication in keratinocytes. Four HPV16 E6 mutations that do not stimulate p53 degradation were unable to support stable viral replication, suggesting this activity may be necessary for episomal maintenance. E7 has also been shown to be essential for episomal maintenance of the HPV31 genome. A point mutation in the Rb binding motif of HPV E7 has been reported to render HPV31 unable to stably replicate. Interestingly, HPV31 genomes harboring two of the three p53 degradation-defective E6 mutations combined with this E7 mutation were maintained as replicating episomes. These findings imply that the balance between E6 and E7 functions in infected cells is critical for episomal maintenance of high-risk HPV genomes. This model will be useful to dissect the activities of E6 and E7 necessary for viral DNA replication.

scholarly journals Molecular characterization of high-risk human papillomavirus (HR-HPV) in women in Lomé, Togo

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Akouélé P. Kuassi-Kpede ◽  
Essolakina Dolou ◽  
Théodora M. Zohoncon ◽  
Ina Marie Angèle Traore ◽  
Gnatoulma Katawa ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
West Africa ◽  
Public Health Problem ◽  
Hpv Infection ◽  
Cervical Lesions ◽  
Hpv Genotypes ◽  
Precancerous Cervical Lesions ◽  
High Risk Hpv ◽  
First Time

Abstract Background The causative agent of cervical cancer referred to as Human papillomavirus (HPV) remains a real public health problem. Many countries in West Africa, such as Togo have no data on the high-risk HPV (HR-HPV) infection and genotypes distribution. In order to fill the knowledge gap in the field in Togo, the main objective of this study was to determine the prevalence of pre-cancerous lesions of the cervix and HR-HPV genotypes among Togolese women. Methods Samples were collected from 240 women by introducing a swab in the cervix. Then, the screening of precancerous cervical lesions using the visual inspection with acetic acid and lugol (VIA / VIL) was conducted. The HR-HPV genotypes were characterised by real-time multiplex PCR. Results Out of 240 women recruited, 128 (53.3%) were infected by HR-HPV. The most common genotypes were HPV 56 (22.7%), followed by HPV 51 (20.3%), HPV 31 (19.5%), HPV 52 (18.8%) and HPV 35 (17.2%). The least common genotypes were HPV 33 (2.3%) and HPV 16 (2.3%). Among the women, 1.3% (3/240) were positive to VIA/VIL. Conclusion This study allowed HR-HPV genotypes to be characterised for the first time in Lomé, Togo. This will help in mapping the HR-HPV genotypes in West Africa.

Prevalence of oropharyngeal high-risk human papillomavirus in tumor-free tonsil tissue in adults

2021 ◽  
pp. 103063
Author(s):  
Erdem Mengi ◽  
Cüneyt Orhan Kara ◽  
Yeliz Arman Karakaya ◽  
Ferda Bir
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Tonsil Tissue
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