Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host
| Autor: | Kim C. Worley, Muthuswamy Raveendran, Mirko Paiardini, Matthew W. Hahn, R. Alan Harris, Gregory K. Tharp, Donald L. Sodora, Daniel Sauter, Guido Silvestri, David Palesch, Reem A. Dawoud, Sara M. Seepo, Richard A. Gibbs, Jeffrey Rogers, Thomas H. Vanderford, Yi Han, Caro-Beth Stewart, Frank Kirchhoff, Gregg W.C. Thomas, Donna M. Muzny, Nirav B. Patel, Ann Chahroudi, Beatrice H. Hahn, Adam C. English, Robert B. Norgren, Yue Liu, Zachary P. Johnson, Christopher E. Mason, Steven E. Bosinger, Lenore Pipes |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Simian Acquired Immunodeficiency Syndrome Genomics medicine.disease_cause Genome Article Host Specificity Frameshift mutation 03 medical and health sciences Cercocebus atys 0302 clinical medicine Species Specificity Genetic variation medicine Animals Humans Genetic Predisposition to Disease Amino Acid Sequence Frameshift Mutation Gene Sequence Deletion Whole genome sequencing Acquired Immunodeficiency Syndrome Multidisciplinary biology Whole Genome Sequencing Genetic Variation HIV Exons Simian immunodeficiency virus biology.organism_classification Virology 3. Good health Toll-Like Receptor 4 030104 developmental biology Sooty mangabey Macaca Female Simian Immunodeficiency Virus Transcriptome Cell Adhesion Molecules 030217 neurology & neurosurgery |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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 viraemia1. 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. |
| Databáze: | OpenAIRE |
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