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      First Detection of an Enterovirus C99 in a Captive Chimpanzee with Acute Flaccid Paralysis, from the Tchimpounga Chimpanzee Rehabilitation Center, Republic of Congo

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          Abstract

          Enteroviruses, members of the Picornaviridae family, are ubiquitous viruses responsible for mild to severe infections in human populations around the world. In 2010 Pointe-Noire, Republic of Congo recorded an outbreak of acute flaccid paralysis (AFP) in the humans, caused by wild poliovirus type 1 (WPV1). One month later, in the Tchimpounga sanctuary near Pointe-Noire, a chimpanzee developed signs similar to AFP, with paralysis of the lower limbs. In the present work, we sought to identify the pathogen, including viral and bacterial agents, responsible for this illness. In order to identify the causative agent, we evaluated a fecal specimen by PCR and sequencing. A Human enterovirus C, specifically of the EV-C99 type was potentially responsible for the illness in this chimpanzee. To rule out other possible causative agents, we also investigated the bacteriome and the virome using next generation sequencing. The majority of bacterial reads obtained belonged to commensal bacteria (95%), and the mammalian virus reads matched mainly with viruses of the Picornaviridae family (99%), in which enteroviruses were the most abundant (99.6%). This study thus reports the first identification of a chimpanzee presenting AFP most likely caused by an enterovirus and demonstrates once again the cross-species transmission of a human pathogen to an ape.

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          Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination.

          The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.
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            Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification.

            Sixty-six human enterovirus serotypes have been identified by serum neutralization, but the molecular determinants of the serotypes are unknown. Since the picornavirus VP1 protein contains a number of neutralization domains, we hypothesized that the VP1 sequence should correspond with neutralization (serotype) and, hence, with phylogenetic lineage. To test this hypothesis and to analyze the phylogenetic relationships among the human enteroviruses, we determined the complete VP1 sequences of the prototype strains of 47 human enterovirus serotypes and 10 antigenic variants. Our sequences, together with those available from GenBank, comprise a database of complete VP1 sequences for all 66 human enterovirus serotypes plus additional strains of seven serotypes. Phylogenetic trees constructed from complete VP1 sequences produced the same four major clusters as published trees based on partial VP2 sequences; in contrast to the VP2 trees, however, in the VP1 trees strains of the same serotype were always monophyletic. In pairwise comparisons of complete VP1 sequences, enteroviruses of the same serotype were clearly distinguished from those of heterologous serotypes, and the limits of intraserotypic divergence appeared to be about 25% nucleotide sequence difference or 12% amino acid sequence difference. Pairwise comparisons suggested that coxsackie A11 and A15 viruses should be classified as strains of the same serotype, as should coxsackie A13 and A18 viruses. Pairwise identity scores also distinguished between enteroviruses of different clusters and enteroviruses from picornaviruses of different genera. The data suggest that VP1 sequence comparisons may be valuable in enterovirus typing and in picornavirus taxonomy by assisting in the genus assignment of unclassified picornaviruses.
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              Pandemic human viruses cause decline of endangered great apes.

              Commercial hunting and habitat loss are major drivers of the rapid decline of great apes [1]. Ecotourism and research have been widely promoted as a means of providing alternative value for apes and their habitats [2]. However, close contact between humans and habituated apes during ape tourism and research has raised concerns that disease transmission risks might outweigh benefits [3-7]. To date only bacterial and parasitic infections of typically low virulence have been shown to move from humans to wild apes [8, 9]. Here, we present the first direct evidence of virus transmission from humans to wild apes. Tissue samples from habituated chimpanzees that died during three respiratory-disease outbreaks at our research site, Côte d'Ivoire, contained two common human paramyxoviruses. Viral strains sampled from chimpanzees were closely related to strains circulating in contemporaneous, worldwide human epidemics. Twenty-four years of mortality data from observed chimpanzees reveal that such respiratory outbreaks could have a long history. In contrast, survey data show that research presence has had a strong positive effect in suppressing poaching around the research site. These observations illustrate the challenge of maximizing the benefit of research and tourism to great apes while minimizing the negative side effects.
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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
                24 August 2015
                2015
                : 10
                : 8
                : e0136700
                Affiliations
                [1 ]Centre International de Recherche Médicale de Franceville, BP769, Franceville, Gabon
                [2 ]Laboratoire MIVEGEC UMR 224–5290 CNRS-IRD-UM1-UM2, IRD, Montpellier, France
                [3 ]Centre National de la Recherche Scientifique, UMR3569, 25 rue du docteur Roux, 75724, Paris, France
                [4 ]Chumakov Institute of Poliomyelitis and Viral Encephalities, Moscow, Russia
                [5 ]Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
                [6 ]The Jane Goodall Institute, Suite 550, 1595 Spring Hill Rd, Vienna, Virginia, 22182, United States of America
                [7 ]Institut Pasteur, Genomic platform, 28, rue du Docteur Roux, F-75724, Paris, France
                [8 ]Metabiota, Inc., 1 Sutter Street, Suite 600, San Francisco, California, 94104, United States of America
                [9 ]CHRU de Montpellier, Montpellier, France
                The Scripps Research Institute, UNITED STATES
                Author notes

                Competing Interests: The authors have the following interests. This work was partly supported by Total Gabon. Joseph N. Fair and Bradley S. Schneider are employed by Metabiota, Inc. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

                Performed the experiments: IMM TB SB CB VR RA DC PD CA LB. Analyzed the data: IMM ANL LL NB. Contributed reagents/materials/analysis tools: EML FR JFD CD FP JNF BSS. Wrote the paper: IMM ANL VR EML.

                ‡ These authors co-managed this work.

                Article
                PONE-D-15-16518
                10.1371/journal.pone.0136700
                4547728
                26301510
                fa44ab9b-0ec9-4798-bd48-578a1e0595eb
                Copyright @ 2015

                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
                : 22 May 2015
                : 6 August 2015
                Page count
                Figures: 3, Tables: 1, Pages: 11
                Funding
                This work was supported by the Gabonese Government, Total Gabon and the ‘Institut National d’Ecologie et d’Evolution’ of CNRS (France). The work was also supported by a fellowship BSTD of the Institut de Recherche pour le Développement (IRD), France, as well as the generous support of the American people through the United States Agency for International Development (USAID) Emerging Pandemic Threats PREDICT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. Metabiota, Inc. provided support in the form of salaries for authors BSS and JNF, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
                Categories
                Research Article
                Custom metadata
                The EV-C99 isolate IJC04 sequence files are available from the GenBank database (accession number KP793035).

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