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

David Palesch, Steven E. Bosinger, Gregory K. Tharp, Thomas H. Vanderford, Mirko Paiardini, Ann Chahroudi, Zachary P. Johnson, Frank Kirchhoff, Beatrice H. Hahn, Robert B. Norgren, Nirav B. Patel, Donald L. Sodora, Reem A. Dawoud, Caro Beth Stewart, Sara M. Seepo, R. Alan Harris, Yue Liu, Muthuswamy Raveendran, Yi Han, Adam EnglishGregg W.C. Thomas, Matthew W. Hahn, Lenore Pipes, Christopher E. Mason, Donna M. Muzny, Richard A. Gibbs, Daniel Sauter, Kim Worley, Jeffrey Rogers, Guido Silvestri

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)77-81
Number of pages5
JournalNature
Volume553
Issue number7686
DOIs
StatePublished - Jan 3 2018

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    Palesch, D., Bosinger, S. E., Tharp, G. K., Vanderford, T. H., Paiardini, M., Chahroudi, A., Johnson, Z. P., Kirchhoff, F., Hahn, B. H., Norgren, R. B., Patel, N. B., Sodora, D. L., Dawoud, R. A., Stewart, C. B., Seepo, S. M., Harris, R. A., Liu, Y., Raveendran, M., Han, Y., ... Silvestri, G. (2018). Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host. Nature, 553(7686), 77-81. https://doi.org/10.1038/nature25140