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      E6/E7 Sequence Diversity of High-Risk Human Papillomaviruses in Two Geographically Isolated Populations of French Guiana

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          Abstract

          Amerindian and Maroon populations of French Guiana have been living in isolation for generations and sexual networks remained mostly endogamous. The present study aimed to describe the phylogeny of E6 and E7 sequences of the most common high-risk HPV genotypes in these regions, to ascertain the diversity of intra-type variants and describe evolutionary relationships. There were 106 women with at least one of HPV16, 18, 31, 52, 58, and 68 genotypes. The most clear-cut phylogenetic pattern was obtained for HPV18 and HPV58 for which the major branches were crisply divided between Amerindian villages on the Oyapock and Maroon villages on the Maroni. Such clustering was less clear for HPV31 and 52. For HPV16, there was also some evidence of clustering on the Oyapock with type A European viruses and on the Maroni with type B and C African viruses among Maroon women. HPV68 showed the largest sequence heterogeneity of the six genotypes at both nucleotide and amino acid levels and was restricted to Maroon women. The present results show that there were significant geographically based differences of E6 and E7 oncogenes. These differences were compatible with different ancestral virus populations and local virus evolution in a context of prolonged population isolation.

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          MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods.

          Comparative analysis of molecular sequence data is essential for reconstructing the evolutionary histories of species and inferring the nature and extent of selective forces shaping the evolution of genes and species. Here, we announce the release of Molecular Evolutionary Genetics Analysis version 5 (MEGA5), which is a user-friendly software for mining online databases, building sequence alignments and phylogenetic trees, and using methods of evolutionary bioinformatics in basic biology, biomedicine, and evolution. The newest addition in MEGA5 is a collection of maximum likelihood (ML) analyses for inferring evolutionary trees, selecting best-fit substitution models (nucleotide or amino acid), inferring ancestral states and sequences (along with probabilities), and estimating evolutionary rates site-by-site. In computer simulation analyses, ML tree inference algorithms in MEGA5 compared favorably with other software packages in terms of computational efficiency and the accuracy of the estimates of phylogenetic trees, substitution parameters, and rate variation among sites. The MEGA user interface has now been enhanced to be activity driven to make it easier for the use of both beginners and experienced scientists. This version of MEGA is intended for the Windows platform, and it has been configured for effective use on Mac OS X and Linux desktops. It is available free of charge from http://www.megasoftware.net.
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            Human papillomavirus genome variants.

            Amongst the human papillomaviruses (HPVs), the genus Alphapapillomavirus contains HPV types that are uniquely pathogenic. They can be classified into species and types based on genetic distances between viral genomes. Current circulating infectious HPVs constitute a set of viral genomes that have evolved with the rapid expansion of the human population. Viral variants were initially identified through restriction enzyme polymorphisms and more recently through sequence determination of viral fragments. Using partial sequence information, the history of variants, and the association of HPV variants with disease will be discussed with the main focus on the recent utilization of full genome sequence information for variant analyses. The use of multiple sequence alignments of complete viral genomes and phylogenetic analyses have begun to define variant lineages and sublineages using empirically defined differences of 1.0-10.0% and 0.5-1.0%, respectively. These studies provide the basis to define the genetics of HPV pathogenesis. © 2013 Elsevier Inc. All rights reserved.
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              Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case-control study.

              Human papillomavirus 16 (HPV16) has a number of variants, each with a different geographic distribution and some that are associated more often with invasive neoplasias. We investigated whether the high incidence of cervical cancer in Mexico (50 cases per 100 000 women) may be associated with a high prevalence of oncogenic HPV16 variants. Cervical samples were collected from 181 case patients with cervical cancer and from 181 age-matched control subjects, all from Mexico City. HPV16 was detected with an E6/E7 gene-specific polymerase chain reaction, and variant HPV classes and subclasses were identified by sequencing regions of the E6 and L1/MY genes. Clinical data and data on tumor characteristics were also collected. All statistical tests were two-sided. HPV16 was detected in cervical scrapes from 50.8% (92 of 181) of case patients and from 11% (20 of 181) of control subjects. All HPV16-positive samples, except one, contained European (E) or Asian-American (AA) variants. AA and E variants were found statistically significantly more often in case patients (AA = 23.2% [42 of 181]; E = 27.1% [49 of 181]) than in control subjects (AA = 1.1% [two of 181]; E = 10% [18 of 181]) (P<.001 for case versus control subjects for either E or AA variants, chi2 test). However, the frequency of AA variants was 21 times higher in cancer patients than in control subjects, whereas that ratio for E variants was only 2.7 (P =.006, chi2 test). The odds ratio (OR) for cervical cancer associated with AA variants (OR = 27.0; 95% confidence interval [CI] = 6.4 to 113.7) was higher than that associated with E variants (OR = 3.4; 95% CI = 1.9 to 6.0). AA-positive case patients (46.2 +/- 12.5 years [mean +/- standard deviation]) were 7.7 years younger than E-positive case patients (53.9 +/- 12.2 years) (P =.004, Student's t test). AA variants were associated with squamous cell carcinomas and adenocarcinomas, but E variants were associated with only squamous cell carcinomas (P =.014, Fisher's exact test). The high frequency of HPV16 AA variants, which appear to be more oncogenic than E variants, might contribute to the high incidence of cervical cancer in Mexico.
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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                23 November 2020
                November 2020
                : 8
                : 11
                : 1842
                Affiliations
                [1 ]Centre d’Investigation Clinique—CIC INSERM 1424, Centre Hospitalier de Cayenne “Andrée Rosemon”, CEDEX 97306 Cayenne, France; valentin.dufit@ 123456ch-cayenne.fr (V.D.); maylis.douine@ 123456ch-cayenne.fr (M.D.); antoine.adenis@ 123456ch-cayenne.fr (A.A.)
                [2 ]Département Formation Recherche Santé, Université de Guyane, Cayenne, CEDEX 97300 Guyane, France
                [3 ]Laboratoire des Interactions Virus-Hôtes, Institut Pasteur de la Guyane, CEDEX 97306 Cayenne, France; gersande.godefroy@ 123456wanadoo.fr (G.G.); vincent.lacoste@ 123456pasteur.fr (V.L.)
                [4 ]Service de Virologie, Martinique University Hospital, Fort-de-France, CEDEX EA, 7524 Martinique, France; fatiha.najioullah@ 123456chu-martinique.fr (F.N.); raymond.cesaire@ 123456chu-martinique.fr (R.C.)
                [5 ]Centres Délocalisés de Prévention et de Soins, Centre Hospitalier de Cayenne “Andrée Rosemon”, CEDEX 97306 Cayenne, France; nf.thomas@ 123456wanadoo.fr
                [6 ]Service d’Anatomopathologie, Centre Hospitalier de Cayenne “Andrée Rosemon”, CEDEX 97306 Cayenne, France; Kdrak.alsibai@ 123456doctor.com
                [7 ]Département de Virologie, Institut Pasteur, CEDEX 75015 Paris, France
                Author notes
                [†]

                Current address: Arbovirus and Emerging Viral Diseases Laboratory, Institut Pasteur du Laos, Vientiane 3560, Laos.

                Author information
                https://orcid.org/0000-0001-9397-3204
                https://orcid.org/0000-0003-4616-6690
                https://orcid.org/0000-0001-5975-2627
                https://orcid.org/0000-0002-3173-4053
                Article
                microorganisms-08-01842
                10.3390/microorganisms8111842
                7700404
                33238632
                91121039-c143-494d-a333-a0f7dabc88e0
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 September 2020
                : 19 November 2020
                Categories
                Article

                human papillomavirus,genotype,variant,remote populations,maroni,oyapock

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