E6 and E7 variants of human papillomavirus‐16 and ‐52 in Japan, the Philippines, and Vietnam

Ishizaki, Azumi; Matsushita, Kazuhiro; Hoang, Huyen Thi Thanh; Agdamag, Dorothy M.; Nguyen, Cong Tien; Tran, Vuong Thi; Sasagawa, Toshiyuki; Saikawa, Kunikazu; Lihana, Raphael; Pham, Hūng Viêt; Bi, Xiuqiong; Ta, Van Thanh; Pham, Thuc Van; Ishiguro, Hiroshi

doi:10.1002/jmv.23566

Cited by 18 publications

(18 citation statements)

References 58 publications

(85 reference statements)

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“…Our findings of the two most frequently detected lineages in HPV52, B and C, also confirm previous observations [19, 20]. These two lineages are associated with high-grade lesions [19, 21], and we have shown that they harbor a number of lineage-specific variations (Tables 2 and 3).…”

Section: Discussionsupporting

confidence: 91%

Analysis of Sequence Variation and Risk Association of Human Papillomavirus 52 Variants Circulating in Korea

Choi

Zhang

et al. 2016

PLoS ONE

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IntroductionHuman papillomavirus (HPV) 52 is a carcinogenic, high-risk genotype frequently detected in cervical cancer cases from East Asia, including Korea.Materials and MethodsSequences of HPV52 detected in 91 cervical samples collected from women attending Seoul St. Mary’s Hospital were analyzed. HPV52 genomic sequences were obtained by polymerase chain reaction (PCR)-based sequencing and analyzed using Seq-Scape software, and phylogenetic trees were constructed using MEGA6 software.ResultsOf the 91 cervical samples, 40 were normal, 22 were low-grade lesions, 21 were high-grade lesions and 7 were squamous cell carcinomas. Four HPV52 variant lineages (A, B, C and D) were identified. Lineage B was the most frequently detected lineage, followed by lineage C. By analyzing the two most frequently detected lineages (B and C), we found that distinct variations existed in each lineage. We also found that a lineage B-specific mutation K93R (A379G) was associated with an increased risk of cervical neoplasia.ConclusionsTo our knowledge, we are the first to reveal the predominance of the HPV52 lineages, B and C, in Korea. We also found these lineages harbored distinct genetic alterations that may affect oncogenicity. Our findings increase our understanding on the heterogeneity of HPV52 variants, and may be useful for the development of new diagnostic assays and therapeutic vaccines.

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Section: Discussionsupporting

confidence: 91%

Analysis of Sequence Variation and Risk Association of Human Papillomavirus 52 Variants Circulating in Korea

Choi

Zhang

et al. 2016

PLoS ONE

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“…For major capsid L1 protein, despite not finding a conservative BCE to cover all HR-HPVs due to about 10% difference of L1 gene among each HPV type 42 , more valuable information is available from Table 2 and Supplementary Table S3 . For example, three of the analyzed 11 conserved BCEs exist within most HR-HPVs including HPV16, 18, 45, and 52 that are prevalent worldwide 33 or in China and Asia 50 , even within two typical LR-HPVs (HPV6 and 11), suggesting that they are potential candidates for designing universal multi-epitope vaccine against major or entire HR-HPVs. Of course, achieving such a goal still requires finding additional conservative BCEs through L1-epitomics study of more HR-HPVs such as HR-HPV16/18/45/52, etc.…”

Section: Discussionmentioning

confidence: 99%

Epitomics: IgG-epitome decoding of E6, E7 and L1 proteins from oncogenic human papillomavirus type 58

Wang

Tang

et al. 2016

Sci Rep

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To enable rational multi-epitope vaccine and diagnostic antigen design, it is imperative to delineate complete IgG-epitome of the protein. Here, we describe results of IgG-epitome decoding of three proteins from high-risk (HR-) oncogenic human papillomavirus type 58 (HPV58). To reveal their entire epitomes, employing peptide biosynthetic approach, 30 precise linear B-cell epitopes (BCEs) were mapped on E6, E7 and L1 proteins using rabbits antisera to the respective recombinant proteins. Using sequence alignment based on BCE minimal motif, the specificity and conservativeness of each mapped BCE were delineated mainly among known HR-HPVs, including finding 3 broadly antibody cross-reactive BCEs of L1 that each covers almost all HR-HPVs. Western blots revealed that 13 of the 18 BCEs within L1-epitome were recognized by murine antisera to HPV58 virus-like particles, suggesting that these are antibody accessible BCEs. Also, a highly conserved epitope (YGD/XTL) of E6 was found to exist only in known common HR-HPVs, which could be used as the first peptide reference marker for judging HR-HPVs. Altogether, this study provides systemic and exhaustive information on linear BCEs of HR-HPV58 that will facilitate development of novel multi-epitope diagnostic reagents/chips for testing viral antibodies and ‘universal’ preventive HPV peptide vaccine based on L1 conserved BCEs.

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“…Additionally, it was notable that the L28F and L83V mutations were commonly associated (50/58, 86.2%). To date, a small number of reports about the L28F mutation have been generated in Japan, Thailand, India, and China . L28F is known to affect DNA synthesis, E2F‐pRb dissociation, pRb binding, and the nuclear localization signal .…”

Section: Discussionmentioning

confidence: 99%

Association of human papillomavirus type 16 and its genetic variants with cervical lesion in Korea

Park

Shin

Kim

et al. 2016

APMIS

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Association of human papillomavirus type 16 and its genetic variants with cervical lesion in Korea. APMIS 2016; 124: 950-957. Persistent human papillomavirus type 16 (HPV16) is the major risk factor for cervical cancer. HPV16 intratypic variants differ in their geographical distribution and oncogenic potential. This study aimed to analyze the distribution of HPV16 variants and their association with cervical lesion histopathology in Korean women. In total, 133 HPV16-positive cervical samples from women admitted to Seoul National University Boramae Hospital were analyzed by sequencing E6, E7, and L1 genes and the long control region (LCR), and the variant distribution according to cervical lesion grade was determined. Isolates were grouped into a phylogenetic lineage, and A1-3, A4, C, and D sublineages were detected in 54.1, 37.8, 0.7, and 7.4% of samples, respectively. The most commonly observed LCR variations were 7521G>A (91.5%), 7730A>C (59.6%), and 7842G>A (59.6%). Furthermore, A4 or D sublineage-positive women had a higher risk for cervical cancer than women who were positive for A1-3. Among HPV phylogenetic clusters, A1-3 was the predominant sublineage, and within A1-3, the 350G polymorphism was highly frequent. These results differed from those of previous studies in Korea and other Asian countries. The findings suggest that cervical neoplasia incidence in HPV16-infected patients could be affected by the distribution of HPV16 variants in the population.Key words: Human papillomavirus 16; variant; cervical cancer; cervical intraepithelial neoplasia; case-control study.Sue Shin, Department of Laboratory Medicine, Seoul National University Boramae Hospital, 156-707, 20 Boramaero-5-gil, Dongjak-gu, Seoul, Korea. e-mail: jeannie@snu.ac.krThe incidence rate of cervical cancer in Korea is higher than that in other developed countries. In 2012, the reported incidence was 14.2 cases per 100 000 women, with 3584 new cases and 889 deaths (1). Persistent infection by oncogenic human papillomaviruses (HPV) is strongly associated with the development of cervical neoplasia. Oncogenic HPV type 16 (HPV16) accounts for approximately 65% of cervical cancer worldwide (2) and is the most common HPV type associated with cervical cancer in Korea (3).The HPV oncogenes, E6 and E7, are consistently expressed in cervical cancers, and these genes are involved in HPV-mediated carcinogenesis (4). Currently, HPV16 intratypic variants, which have nucleotide sequence variations of ≤2% as compared with the HPV16 prototype, are classified into four major lineages based on whole-genome sequencing: A, which includes the A1-3 (previously named European), and A4 (Asian) sublineages; B (African 1); C (African 2); and D [including Asian-American (AA) and North American (NA)] (5). The long control region (LCR) adjacent to the downstream region of E6 contains the early promoter and regulatory elements involved in viral DNA replication and transcription (6). Epidemiological studies have reported that HPV16 variants confer different risks of vira...

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E6 and E7 variants of human papillomavirus‐16 and ‐52 in Japan, the Philippines, and Vietnam

Cited by 18 publications

References 58 publications

Analysis of Sequence Variation and Risk Association of Human Papillomavirus 52 Variants Circulating in Korea

Analysis of Sequence Variation and Risk Association of Human Papillomavirus 52 Variants Circulating in Korea

Epitomics: IgG-epitome decoding of E6, E7 and L1 proteins from oncogenic human papillomavirus type 58

Association of human papillomavirus type 16 and its genetic variants with cervical lesion in Korea

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