September 22, 2019  |  

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

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

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.

Journal: Nature
DOI: 10.1038/nature25140
Year: 2018

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