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Whole Genome Sequencing and Evolutionary Analysis of Human Papillomavirus Type 16 in Central China

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
PLoS ONE (Impact Factor: 3.53). 05/2012; 7(5):e36577. DOI: 10.1371/journal.pone.0036577
Source: PubMed

ABSTRACT Human papillomavirus type 16 plays a critical role in the neoplastic transformation of cervical cancers. Molecular variants of HPV16 existing in different ethnic groups have shown substantial phenotypic differences in pathogenicity, immunogenicity and tumorigenicity. In this study, we sequenced the entire HPV16 genome of 76 isolates originated from Anyang, central China. Phylogenetic analysis of these sequences identified two major variants of HPV16 in the Anyang area, namely the European prototype (E(p)) and the European Asian type (E(As)). These two variants show a high degree of divergence between groups, and the E(p) comprised higher genetic diversity than the E(As). Analysis with two measurements of genetic diversity indicated that viral population size was relatively stable in this area in the past. Codon based likelihood models revealed strong statistical support for adaptive evolution acting on the E6 gene. Bayesian analysis identified several important amino acid positions that may be driving adaptive selection in the HPV 16 population, including R10G, D25E, L83V, and E113D in the E6 gene. We hypothesize that the positive selection at these codons might be a contributing factor responsible for the phenotypic differences in carcinogenesis and immunogenicity among cervical cancers in China based on the potential roles of these molecular variants reported in other studies.

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    • "Some specific amino acid mutations in HPV-16 E6 have been reported to be associated with a greater capacity for carcinogenesis. The European (Asian) sublineage characterized by D25E [Sun et al., 2012], European (Prototype) sublineage with L83V, non-European lineage with Q14H/H78Y/L83V (corresponding to the African-1 and -2, Asian-American-1 and -2, and North American 1 sublineages) [Lizano et al., 2009; Zehbe et al., 2009; Richard et al., 2010; Schiffman et al., 2010; Chansaenroj et al., 2012], and HPV-16 E7 N29S mutations are considered to be related to the development of cervical cancer in Asian populations [Chan et al., 2002; Choi et al., 2007; Lee et al., 2011; Chansaenroj et al., 2012]. However, no significant correlation between abnormal cervical cytology and intragenotypic variations of either HPV- 16 or -52 sublineages or between abnormal cervical cytology and the specific amino acid mutations at HPV-16 E6 D25E, E6 L83V, and E7 N29S was observed in the current study. "
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    ABSTRACT: Human papillomavirus (HPV) has several intragenotypic variants with different geographical and ethnic distributions. This study aimed to elucidate the distribution patterns of E6 and E7 (E6/E7) intragenotypic variants of HPV type 16 (HPV-16), which is most common worldwide, and HPV-52, which is common in Asian countries such as Japan, the Philippines, and Vietnam. In previous studies, genomic DNA samples extracted from cervical swabs were collected from female sex workers in these three countries and found to be positive for HPV-16 or HPV-52. Samples were amplified further for their E6/E7 genes using type-specific primers and analyzed genetically. Seventy-nine HPV-16 E6/E7 genes were analyzed successfully and grouped into three lineages: European (Prototype), European (Asian), and African-2. The prevalences of HPV-16 European (Prototype)/European (Asian) lineages were 19.4%/80.6% (n = 31) in Japan, 75.0%/20.8% (n = 24) in the Philippines, and 0%/95.8% (n = 24) in Vietnam. The 109 HPV-52 E6/E7 genes analyzed successfully were grouped into four lineages, A-D; the prevalences of lineages A/B/C/D were, respectively, 5.1%/92.3%/0%/2.6% in Japan (n = 39), 34.4%/62.5%/0%/3.1% in the Philippines (n = 32), and 15.8%/73.7%/7.9%/2.6% in Vietnam (n = 38). The distribution patterns of HPV-16 and HPV-52 lineages in these countries differed significantly (P < 0.000001 and P = 0.0048, respectively). There was no significant relationship between abnormal cervical cytology and either HPV-16 E6/E7 lineages or specific amino acid mutations, such as E6 D25E, E6 L83V, and E7 N29S. Analysis of HPV-16 and HPV-52 E6/E7 genes can be a useful molecular-epidemiological tool to distinguish geographical diffusion routes of these HPV types in Asia. J. Med. Virol. 85: 1069-1076, 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2013; 85(6):1069-76. DOI:10.1002/jmv.23566 · 2.22 Impact Factor
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    • "Some specific amino acid mutations in HPV-16 E6 have been reported to be associated with a greater capacity for carcinogenesis. The European (Asian) sublineage characterized by D25E [Sun et al., 2012], European (Prototype) sublineage with L83V, non-European lineage with Q14H/H78Y/L83V (corresponding to the African-1 and -2, Asian-American-1 and -2, and North American 1 sublineages) [Lizano et al., 2009; Zehbe et al., 2009; Richard et al., 2010; Schiffman et al., 2010; Chansaenroj et al., 2012], and HPV-16 E7 N29S mutations are considered to be related to the development of cervical cancer in Asian populations [Chan et al., 2002; Choi et al., 2007; Lee et al., 2011; Chansaenroj et al., 2012]. However, no significant correlation between abnormal cervical cytology and intragenotypic variations of either HPV- 16 or -52 sublineages or between abnormal cervical cytology and the specific amino acid mutations at HPV-16 E6 D25E, E6 L83V, and E7 N29S was observed in the current study. "
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    ABSTRACT: Scrub typhus, an acute febrile illness, is caused by the obligate intracellular bacterium Orientia tsutsugamushi. In our study, O. tsutsugamushi was rapidly detected and typed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis of the 56-kDa type-specific antigen (TSA) gene. To investigate the genotypes of clinical variants of O. tsutsugamushi, we collected 3223 blood samples from eastern Taiwanese patients with suspected scrub typhus from 2002 to 2008. In total, 505 samples were found to be positive for scrub typhus infection by PCR, and bacteria were isolated from 282 of them. Four prototype genotype strains (Karp, Kato, Kawasaki and Gilliam) and eleven different Taiwanese genotype isolates (Taiwan-A, -B, -C, -D, -E, -G, -H, -J, -N, -O and -P) were identified by RPLF analysis. Taiwan-H, the major genotype in eastern Taiwan, exhibited prevalence and isolation rates of 47.3% (239/505) and 42.6% (120/282), respectively. We also assessed the genetic relatedness of the 56-kDa TSA gene among eight Taiwan-H isolates, thirteen other Taiwanese isolates and 104 DNA sequences deposited in the GenBank database using MEGA version 5.0 and PHYLIP version 3.66. We found that the Taiwan-H isolates formed into a new cluster, which was designated the Taiwan Gilliam-variant (TG-v) cluster to distinguish it from the Japanese Gilliam-variant (JG-v) cluster. According to Simplot analysis, TG-v is a new recombinant strain among Gilliam, Ikeda and Kato. Moreover, the Gilliam-Kawasaki cluster had the highest percentage of RFLP cases and was the most frequently isolated type in eastern Taiwan (50.1%, 253/505; 44.0%, 124/282). These findings shed light on the genetic evolution of O. tsutsugamushi into different strains and may be useful in vaccine development and epidemic disease control in the future.
    PLoS ONE 10/2012; 7(10):e46997. DOI:10.1371/journal.pone.0046997 · 3.53 Impact Factor
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