scholarly journals High Levels of Within-Host Variations of Human Papillomavirus 16 E1/E2 Genes in Invasive Cervical Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Yusuke Hirose ◽  
Mayuko Yamaguchi-Naka ◽  
Mamiko Onuki ◽  
Yuri Tenjimbayashi ◽  
Nobutaka Tasaka ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Viral Replication ◽  
Viral Genome ◽  
Invasive Cervical Cancer ◽  
Infected Woman ◽  
Human Papillomavirus 16 ◽  
Normal Cervix ◽  
High Level

Human papillomavirus type 16 (HPV16) is the most common HPV genotype found in invasive cervical cancer (ICC). Recent comprehensive genomics studies of HPV16 have revealed that a large number of minor nucleotide variations in the viral genome are present in each infected woman; however, it remains unclear whether such within-host variations of HPV16 are linked to cervical carcinogenesis. Here, by employing next-generation sequencing approaches, we explored the mutational profiles of the HPV16 genome within individual clinical specimens from ICC (n = 31) and normal cervix (n = 21) in greater detail. A total of 367 minor nucleotide variations (167 from ICC and 200 from the normal cervix) were detected throughout the viral genome in both groups, while nucleotide variations at high frequencies (>10% abundance in relative read counts in a single sample) were more prevalent in ICC (10 in ICC versus 1 in normal). Among the high-level variations found in ICC, six were located in the E1/E2 genes, and all of them were non-synonymous substitutions (Q142K, M207I, and L262V for E1; D153Y, R302T, and T357A for E2). In vitro functional analyses of these E1/E2 variants revealed that E1/M207I, E2/D153Y, and E2/R302T had reduced abilities to support viral replication, and that E2/D153Y and E2/R302T failed to suppress the viral early promoter. These results imply that some within-host variations of E1/E2 present at high levels in ICC may be positively selected for and contribute to cervical cancer development through dysfunction or de-stabilization of viral replication/transcription proteins.

scholarly journals Whole-Genome Sequencing and Variant Analysis of Human Papillomavirus 16 Infections

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
Pascal van der Weele ◽  
Chris J. L. M. Meijer ◽  
Audrey J. King
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Progression ◽  
Viral Genome ◽  
Sequence Diversity ◽  
Whole Genome ◽  
Human Papillomavirus 16 ◽  
Persistent Infections ◽  
Hpv16 Infection

ABSTRACT Human papillomavirus (HPV) is a strongly conserved DNA virus, high-risk types of which can cause cervical cancer in persistent infections. The most common type found in HPV-attributable cancer is HPV16, which can be subdivided into four lineages (A to D) with different carcinogenic properties. Studies have shown HPV16 sequence diversity in different geographical areas, but only limited information is available regarding HPV16 diversity within a population, especially at the whole-genome level. We analyzed HPV16 major variant diversity and conservation in persistent infections and performed a single nucleotide polymorphism (SNP) comparison between persistent and clearing infections. Materials were obtained in the Netherlands from a cohort study with longitudinal follow-up for up to 3 years. Our analysis shows a remarkably large variant diversity in the population. Whole-genome sequences were obtained for 57 persistent and 59 clearing HPV16 infections, resulting in 109 unique variants. Interestingly, persistent infections were completely conserved through time. One reinfection event was identified where the initial and follow-up samples clustered differently. Non-A1/A2 variants seemed to clear preferentially (P = 0.02). Our analysis shows that population-wide HPV16 sequence diversity is very large. In persistent infections, the HPV16 sequence was fully conserved. Sequencing can identify HPV16 reinfections, although occurrence is rare. SNP comparison identified no strongly acting effect of the viral genome affecting HPV16 infection clearance or persistence in up to 3 years of follow-up. These findings suggest the progression of an early HPV16 infection could be host related. IMPORTANCE Human papillomavirus 16 (HPV16) is the predominant type found in cervical cancer. Progression of initial infection to cervical cancer has been linked to sequence properties; however, knowledge of variants circulating in European populations, especially with longitudinal follow-up, is limited. By sequencing a number of infections with known follow-up for up to 3 years, we gained initial insights into the genetic diversity of HPV16 and the effects of the viral genome on the persistence of infections. A SNP comparison between sequences obtained from clearing and persistent infections did not identify strongly acting DNA variations responsible for these infection outcomes. In addition, we identified an HPV16 reinfection event where sequencing of initial and follow-up samples showed different HPV16 variants. Based on conventional genotyping, this infection would incorrectly be considered a persistent HPV16 infection. In the context of vaccine efficacy and monitoring studies, such infections could potentially cause reduced reported efficacy or efficiency.

scholarly journals Human papillomavirus 16 sub-lineage dispersal and cervical cancer risk worldwide: Whole viral genome sequences from 7116 HPV16-positive women

2019 ◽  
Vol 7 ◽  
pp. 67-74 ◽  
Author(s):  
Gary M. Clifford ◽  
Vanessa Tenet ◽  
Damien Georges ◽  
Laia Alemany ◽  
Miquel Angel Pavón ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Risk ◽  
Viral Genome ◽  
Genome Sequences ◽  
Human Papillomavirus 16 ◽  
Cervical Cancer Risk

scholarly journals In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by e6 siRNA

2003 ◽  
Vol 8 (5) ◽  
pp. 762-768 ◽  
Author(s):  
Mitsuo Yoshinouchi ◽  
Taketo Yamada ◽  
Masahiro Kizaki ◽  
Jin Fen ◽  
Takeyoshi Koseki ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Cells ◽  
Growth Suppression ◽  
Human Papillomavirus 16 ◽  
Cervical Cancer Cells ◽  
In Vivo Growth

scholarly journals Prognostic significance of serum antibodies to human papillomavirus-16 E4 and E7 peptides in cervical cancer

Cancer ◽  
1994 ◽  
Vol 74 (8) ◽  
pp. 2307-2313 ◽  
Author(s):  
Katja N. Gaarenstroom ◽  
Gemma G. Kenter ◽  
J. Baptist Trimbos ◽  
Johannes M. G. Bonfrer ◽  
Catharina M. Korse ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Prognostic Significance ◽  
Serum Antibodies ◽  
Human Papillomavirus 16

scholarly journals Synergistic In Vitro Antiretroviral Activity of a Humanized Monoclonal Anti-CD4 Antibody (TNX-355) and Enfuvirtide (T-20)

2006 ◽  
Vol 50 (6) ◽  
pp. 2231-2233 ◽  
Author(s):  
Xing-Quan Zhang ◽  
Meredith Sorensen ◽  
Michael Fung ◽  
Robert T. Schooley
Keyword(s):  
Viral Replication ◽  
Viral Entry ◽  
Antiretroviral Agents ◽  
Entry Inhibitors ◽  
High Level ◽  
Antiretroviral Activity

ABSTRACT Recently, antiretroviral agents directed at several steps involved in viral entry have been shown to reduce viral replication in vitro and in vivo. We have demonstrated a high level of in vitro synergistic antiretroviral activity for two entry inhibitors that are directed at sequential steps in the entry process.

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