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

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(1). Here we sequenced and assembled the genome of a captive soo...

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Detalles Bibliográficos
Autores principales: Palesch, David, Bosinger, Steven E., Tharp, Gregory K., Vanderford, Thomas H., Paiardini, Mirko, Chahroudi, Ann, Johnson, Zachary P., Kirchhoff, Frank, Hahn, Beatrice H., Norgren, Robert B., Patel, Nirav B., Sodora, Donald L., Dawoud, Reem A., Stewart, Caro-Beth, Seepo, Sara M., Harris, R. Alan, Liu, Yue, Raveendran, Muthuswamy, Han, Yi, English, Adam, Thomas, Gregg W. C., Hahn, Matthew W., Pipes, Lenore, Mason, Christopher E., Muzny, Donna M., Gibbs, Richard A., Sauter, Daniel, Worley, Kim, Rogers, Jeffrey, Silvestri, Guido
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843367/
https://www.ncbi.nlm.nih.gov/pubmed/29300007
http://dx.doi.org/10.1038/nature25140
Descripción
Sumario: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(1). 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.