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

TitleSooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host.
Publication TypeJournal Article
Year of Publication2018
AuthorsPalesch, 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
JournalNature
Volume553
Issue7686
Pagination77-81
Date Published2018 Jan 03
ISSN1476-4687
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.

DOI10.1038/nature25140
Alternate JournalNature
PubMed ID29300007
PubMed Central IDPMC5843367
Grant ListP30 AI050409 / AI / NIAID NIH HHS / United States
P51 OD011132 / OD / NIH HHS / United States
R37 AI050529 / AI / NIAID NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
R37 AI066998 / AI / NIAID NIH HHS / United States
R24 OD010445 / OD / NIH HHS / United States
R01 AI066998 / AI / NIAID NIH HHS / United States