Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host.

Bibliographic Collection: 
CARTA-Inspired Publication
Publication Type: Journal Article
Authors: Palesch, D; Bosinger, SE; Tharp, GK; Vanderford, TH; Paiardini, M; Chahroudi, A; Johnson, ZP; Kirchhoff, F; Hahn, BH; Norgren, RB; Patel, NB; Sodora, DL; Dawoud, RA; Stewart, CB; Seepo, SM; Harris, RA; Liu, Y; Raveendran, M; Han, Y; English, A; Thomas, GWC; Hahn, MW; Pipes, L; Mason, CE; Muzny, DM; Gibbs, RA; Sauter, D; Worley, K; Rogers, J; Silvestri, G
Year of Publication: 2018
Journal: Nature
Volume: 553
Number: 7686
Pagination: 77-81
Date Published: 01/
Publication Language: eng
ISBN Number: 0028-0836
Accession Number: 29300007
Abstract:

In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a C-terminal frameshift in the toll-like receptor-4 (TLR4) gene of C. atys, is associated with a blunted in vitro response to TLR-4 ligands. In addition, we found a major structural change in exons 3-4 of the immune-regulatory protein intercellular adhesion molecule 2 (ICAM-2); expression of this variant leads to reduced cell surface expression of ICAM-2. These data provide a resource for comparative genomic studies of HIV and/or SIV pathogenesis and may help to elucidate the mechanisms by which SIV-infected sooty mangabeys avoid AIDS.

Author Address:

Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30329, USA. Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA. Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA. Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30329, USA. Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA. Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30329, USA. Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA. Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany. Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. Department of Genetics, Cell Biology and Anatomy, University of Nebraska, Medical Center, Omaha, Nebraska 68198, USA. Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA. Center for Infectious Disease Research, formerly Seattle Biomedical Research Institute, Seattle, Washington 98109, USA. Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA. Department of Biological Sciences, University at Albany-State University of New York, Albany, New York 12222, USA. Department of Biological Sciences, University at Albany-State University of New York, Albany, New York 12222, USA. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. Department of Biology and School of Informatics and Computing, Indiana University, Bloomington, Indiana 47405, USA. Department of Biology and School of Informatics and Computing, Indiana University, Bloomington, Indiana 47405, USA. Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA. Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30329, USA.

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