|Title||Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|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, C-B, Seepo, SM, R Harris, A, 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|
|Date Published||2018 Jan 03|
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.