Characterization and Whole Genome Analysis of Human Papillomavirus Type 16 E1-1374∧63nt Variants
Identifieur interne : 000263 ( Main/Exploration ); précédent : 000262; suivant : 000264Characterization and Whole Genome Analysis of Human Papillomavirus Type 16 E1-1374∧63nt Variants
Auteurs : Ivan Sabol [Croatie] ; Mihaela Matovina [Croatie] ; Ali Si-Mohamed [France] ; Magdalena Grce [Croatie]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
The variation of the most common Human papillomavirus (HPV) type found in cervical cancer, the HPV16, has been extensively investigated in almost all viral genes. The E1 gene variation, however, has been rarely studied. The main objective of the present investigation was to analyze the variability of the E6 and E1 genes, focusing on the recently identified E1-1374∧63nt variant.
Variation within the E6 of 786 HPV16 positive cervical samples was analyzed using high-resolution melting, while the E1-1374∧63nt duplication was assayed by PCR. Both techniques were supplemented with sequencing. The E1-1374∧63nt duplication was linked with the E-G350 and the E-C109/G350 variants. In comparison to the referent HPV16, the E1-1374∧63nt E-G350 variant was significantly associated with lower grade cervical lesions (p = 0.029), while the E1-1374∧63nt E-C109/G350 variant was equally distributed between high and low grade lesions. The E1-1374∧63nt variants were phylogenetically closest to E-G350 variant lineage (A2 sub-lineage based on full genome classification). The major differences between E1-1374∧63nt variants were within the LCR and the E6 region. On the other hand, changes within the E1 region were the major differences from the A2 sub-lineage, which has been historically but inconclusively associated with high grade cervical disease. Thus, the shared variations cannot explain the particular association of the E1-1374∧63nt variant with lower grade cervical lesions.
The E1 region has been thus far considered to be well conserved among all HPVs and therefore uninteresting for variability studies. However, this study shows that the variations within the E1 region could possibly affect cervical disease, since the E1-1374∧63nt E-G350 variant is significantly associated with lower grade cervical lesions, in comparison to the A1 and A2 sub-lineage variants. Furthermore, it appears that the silent variation 109T>C of the E-C109/G350 variant might have a significant role in the viral life cycle and warrants further study.
Url:
DOI: 10.1371/journal.pone.0041045
PubMed: 22911739
PubMed Central: 3404080
Affiliations:
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xml:lang="fr">Croatie</country><wicri:regionArea>Department of Microbiology and Parasitology, School of Medicine, University of Rijeka, Rijeka</wicri:regionArea><wicri:noRegion>Rijeka</wicri:noRegion></affiliation></author><author><name sortKey="Si Mohamed, Ali" sort="Si Mohamed, Ali" uniqKey="Si Mohamed A" first="Ali" last="Si-Mohamed">Ali Si-Mohamed</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Grce, Magdalena" sort="Grce, Magdalena" uniqKey="Grce M" first="Magdalena" last="Grce">Magdalena Grce</name><affiliation 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Medicine, Rudjer Boskovic Institute, Zagreb</wicri:regionArea><wicri:noRegion>Zagreb</wicri:noRegion></affiliation></author><author><name sortKey="Matovina, Mihaela" sort="Matovina, Mihaela" uniqKey="Matovina M" first="Mihaela" last="Matovina">Mihaela Matovina</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Microbiology and Parasitology, School of Medicine, University of Rijeka, Rijeka, Croatia</addr-line></nlm:aff><country xml:lang="fr">Croatie</country><wicri:regionArea>Department of Microbiology and Parasitology, School of Medicine, University of Rijeka, Rijeka</wicri:regionArea><wicri:noRegion>Rijeka</wicri:noRegion></affiliation></author><author><name sortKey="Si Mohamed, Ali" sort="Si Mohamed, Ali" uniqKey="Si Mohamed A" first="Ali" last="Si-Mohamed">Ali Si-Mohamed</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Grce, Magdalena" sort="Grce, Magdalena" uniqKey="Grce M" first="Magdalena" last="Grce">Magdalena Grce</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia</addr-line></nlm:aff><country xml:lang="fr">Croatie</country><wicri:regionArea>Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb</wicri:regionArea><wicri:noRegion>Zagreb</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The variation of the most common Human papillomavirus (HPV) type found in cervical cancer, the HPV16, has been extensively investigated in almost all viral genes. The E1 gene variation, however, has been rarely studied. The main objective of the present investigation was to analyze the variability of the E6 and E1 genes, focusing on the recently identified E1-1374<sup>∧</sup>63nt variant.</p></sec><sec><title>Methodology/Principal Findings</title><p>Variation within the E6 of 786 HPV16 positive cervical samples was analyzed using high-resolution melting, while the E1-1374<sup>∧</sup>63nt duplication was assayed by PCR. Both techniques were supplemented with sequencing. The E1-1374<sup>∧</sup>63nt duplication was linked with the E-G350 and the E-C109/G350 variants. In comparison to the referent HPV16, the E1-1374<sup>∧</sup>63nt E-G350 variant was significantly associated with lower grade cervical lesions (p = 0.029), while the E1-1374<sup>∧</sup>63nt E-C109/G350 variant was equally distributed between high and low grade lesions. The E1-1374<sup>∧</sup>63nt variants were phylogenetically closest to E-G350 variant lineage (A2 sub-lineage based on full genome classification). The major differences between E1-1374<sup>∧</sup>63nt variants were within the LCR and the E6 region. On the other hand, changes within the E1 region were the major differences from the A2 sub-lineage, which has been historically but inconclusively associated with high grade cervical disease. Thus, the shared variations cannot explain the particular association of the E1-1374<sup>∧</sup>63nt variant with lower grade cervical lesions.</p></sec><sec><title>Conclusions/Significance</title><p>The E1 region has been thus far considered to be well conserved among all HPVs and therefore uninteresting for variability studies. However, this study shows that the variations within the E1 region could possibly affect cervical disease, since the E1-1374<sup>∧</sup>63nt E-G350 variant is significantly associated with lower grade cervical lesions, in comparison to the A1 and A2 sub-lineage variants. Furthermore, it appears that the silent variation 109T>C of the E-C109/G350 variant might have a significant role in the viral life cycle and warrants further study.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mu Oz, N" uniqKey="Mu Oz N">N Muñoz</name></author><author><name sortKey="Bosch, Fx" uniqKey="Bosch F">FX Bosch</name></author><author><name sortKey="De Sanjose, S" uniqKey="De Sanjose S">S de Sanjose</name></author><author><name sortKey="Herrero, R" uniqKey="Herrero R">R Herrero</name></author><author><name sortKey="Castellsague, X" uniqKey="Castellsague X">X Castellsague</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bernard, H U" uniqKey="Bernard H">H-U Bernard</name></author><author><name sortKey="Calleja Macias, Ie" uniqKey="Calleja Macias I">IE Calleja-Macias</name></author><author><name sortKey="Dunn, St" uniqKey="Dunn S">ST 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Jordan</name></author><author><name sortKey="Williamson, Aj" uniqKey="Williamson A">AJ Williamson</name></author><author><name sortKey="Brown, M" uniqKey="Brown M">M Brown</name></author><author><name sortKey="Coote, Jh" uniqKey="Coote J">JH Coote</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fu, C" uniqKey="Fu C">C Fu</name></author><author><name sortKey="Parker, J" uniqKey="Parker J">J Parker</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Croatie</li><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><country name="Croatie"><noRegion><name sortKey="Sabol, Ivan" sort="Sabol, Ivan" uniqKey="Sabol I" first="Ivan" last="Sabol">Ivan Sabol</name></noRegion><name sortKey="Grce, Magdalena" sort="Grce, Magdalena" uniqKey="Grce M" first="Magdalena" last="Grce">Magdalena Grce</name><name sortKey="Matovina, Mihaela" sort="Matovina, Mihaela" uniqKey="Matovina M" first="Mihaela" last="Matovina">Mihaela Matovina</name></country><country name="France"><region name="Île-de-France"><name sortKey="Si Mohamed, Ali" sort="Si Mohamed, Ali" uniqKey="Si Mohamed A" first="Ali" last="Si-Mohamed">Ali Si-Mohamed</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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