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      High Prevalence and Onward Transmission of Non-Pandemic HIV-1 Subtype B Clades in Northern and Northeastern Brazilian Regions

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          Abstract

          The Human immunodeficiency virus type-1 (HIV-1) epidemic in Brazil is mainly driven by the subtype B pandemic lineage (B PANDEMIC), while Caribbean non-pandemic subtype B clades (B CAR) seem to account for a very low fraction of HIV-infections in this country. The molecular characteristics of the HIV-1 subtype B strains disseminated in the Northern and Northeastern Brazilian regions, however, have not been explored so far. In this study, we estimate the prevalence of the HIV-1 B PANDEMIC and B CAR clades across different Brazilian regions and we reconstruct the spatiotemporal dynamics of dissemination of the major Brazilian B CAR clades. A total of 2,682 HIV-1 subtype B pol sequences collected from 21 different Brazilian states from the five country regions between 1998 and 2013 were analyzed. Maximum Likelihood phylogenetic analyses revealed that the B CAR strains reached 16 out 21 Brazilian states here analyzed. The B CAR clades comprise a low fraction (<10%) of subtype B infections in most Brazilian states analyzed, with exception of Roraima (41%), Amazonas (14%) and Maranhão (14%). Bayesian phylogeographic analyses indicate that B CAR strains originally from the Hispaniola and Trinidad and Tobago were introduced at multiple times into different states from all Brazilian regions and a few of those strains, probably introduced into Roraima, Maranhão and São Paulo between the late 1970s and the early 1980s, established secondary outbreaks in the Brazilian population. These results support that the HIV-1 subtype B epidemics in some Brazilian states from the Northern and Northeastern regions display a unique molecular pattern characterized by the high prevalence of B CAR lineages, which probably reflects a strong epidemiological link with the HIV-1 epidemics in the Caribbean region.

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          PHYML Online—a web server for fast maximum likelihood-based phylogenetic inference

          PHYML Online is a web interface to PHYML, a software that implements a fast and accurate heuristic for estimating maximum likelihood phylogenies from DNA and protein sequences. This tool provides the user with a number of options, e.g. nonparametric bootstrap and estimation of various evolutionary parameters, in order to perform comprehensive phylogenetic analyses on large datasets in reasonable computing time. The server and its documentation are available at .
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            Estimating mutation parameters, population history and genealogy simultaneously from temporally spaced sequence data.

            Molecular sequences obtained at different sampling times from populations of rapidly evolving pathogens and from ancient subfossil and fossil sources are increasingly available with modern sequencing technology. Here, we present a Bayesian statistical inference approach to the joint estimation of mutation rate and population size that incorporates the uncertainty in the genealogy of such temporally spaced sequences by using Markov chain Monte Carlo (MCMC) integration. The Kingman coalescent model is used to describe the time structure of the ancestral tree. We recover information about the unknown true ancestral coalescent tree, population size, and the overall mutation rate from temporally spaced data, that is, from nucleotide sequences gathered at different times, from different individuals, in an evolving haploid population. We briefly discuss the methodological implications and show what can be inferred, in various practically relevant states of prior knowledge. We develop extensions for exponentially growing population size and joint estimation of substitution model parameters. We illustrate some of the important features of this approach on a genealogy of HIV-1 envelope (env) partial sequences.
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              SPREAD: spatial phylogenetic reconstruction of evolutionary dynamics

              Summary: SPREAD is a user-friendly, cross-platform application to analyze and visualize Bayesian phylogeographic reconstructions incorporating spatial–temporal diffusion. The software maps phylogenies annotated with both discrete and continuous spatial information and can export high-dimensional posterior summaries to keyhole markup language (KML) for animation of the spatial diffusion through time in virtual globe software. In addition, SPREAD implements Bayes factor calculation to evaluate the support for hypotheses of historical diffusion among pairs of discrete locations based on Bayesian stochastic search variable selection estimates. SPREAD takes advantage of multicore architectures to process large joint posterior distributions of phylogenies and their spatial diffusion and produces visualizations as compelling and interpretable statistical summaries for the different spatial projections. Availability: SPREAD is licensed under the GNU Lesser GPL and its source code is freely available as a GitHub repository: https://github.com/phylogeography/SPREAD Contact: filip.bielejec@rega.kuleuven.be
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 September 2016
                2016
                : 11
                : 9
                : e0162112
                Affiliations
                [1 ]Laboratório de AIDS e Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil
                [2 ]Instituto Leônidas e Maria Deane, Fundação Oswaldo Cruz, Manaus, AM, Brazil
                [3 ]Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO, Brazil
                National Institute of Health, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceived and designed the experiments: GB.

                • Performed the experiments: FD ALGC.

                • Analyzed the data: FD ALGC FGN MMAS GB.

                • Contributed reagents/materials/analysis tools: ALGC FGN MMAS.

                • Wrote the paper: GB FD.

                Article
                PONE-D-16-26700
                10.1371/journal.pone.0162112
                5014447
                27603317
                6dae16c7-4de1-4dee-82b4-43a80a97ac49
                © 2016 Divino et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 4 July 2016
                : 23 July 2016
                Page count
                Figures: 3, Tables: 2, Pages: 14
                Funding
                Funded by: FAPERJ
                Award ID: E-26/110.439/2014
                Award Recipient :
                Funded by: CNPq
                Award ID: 472896/2012-1
                Award Recipient :
                GB was supported by Public Health Service grants E-26/110.439/2014 from the “Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro” (FAPERJ) and 472896/2012-1 from the “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq). FD was funded by a fellowship from Instituto Oswaldo Cruz -FIOCRUZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Custom metadata
                Sequences data were deposited in GenBank under accession numbers KX443015-KX443025, KX443027-KX443059 and KX443061- KX443087.

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