Journal
NATURE
Volume 553, Issue 7686, Pages 77-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/nature25140
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Funding
- HHS/National Institutes of Health (NIH) [R37 AI66998]
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [P51 OD011132]
- NIH [U54-HG006484-01, R37 AI050529, R24 OD010445]
- Priority Program 'Innate Sensing and Restriction of Retroviruses' of the German Research Foundation (DFG) [SPP 1923]
- Advanced ERC grant 'Anti-Virome'
- DFG [SFB 1279]
- Precision Health Initiative of Indiana University
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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.
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