@article{6266debcd9d143c599db93f54d98b12d,
title = "Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host",
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.",
author = "David Palesch and Bosinger, {Steven E.} and Tharp, {Gregory K.} and Vanderford, {Thomas H.} and Mirko Paiardini and Ann Chahroudi and Johnson, {Zachary P.} and Frank Kirchhoff 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 Yue Liu and Muthuswamy Raveendran and Yi Han and Adam English and Thomas, {Gregg W.C.} and Hahn, {Matthew W.} and Lenore Pipes and Mason, {Christopher E.} and Muzny, {Donna M.} and Gibbs, {Richard A.} and Daniel Sauter and Kim Worley and Jeffrey Rogers and Guido Silvestri",
note = "Funding Information: Acknowledgements We thank S. Ehnert and all animal care and veterinary staff at the Yerkes National Primate Research Center (YNPRC); B. Cervasi and K. Gill at the Emory University Flow Cytometry Core; M. T. Nega at the Emory CFAR Virology & Drug Discovery Core; R. Linsenmeyer for excellent technical assistance; and O. Laur and the Emory Custom Cloning Core Division. We are grateful for the sequence production and related activities at the Human Genome Sequencing Center at Baylor College of Medicine. The production teams involved were: sample tracking (S. Jhangiani, C. Kovar), library production (H. Doddapaneni, H. Chao, S. L. Lee, G. Weissenberger and M. Wang), Illumina sequencing (H. Dinh, G. Okwuonu and J. Santibanez), PacBio sequencing (V. Vee) and production informatics (M. Dahdouli, Z. Khan, J. G. Reid and D. Sexton). D. Rio Derios and S. C. Murali also contributed to the assembly of the genome sequence. This work was funded by HHS/National Institutes of Health (NIH) (R37 AI66998). Research reported in this publication was also supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number P51 OD011132 (to the YNPRC). D.M.M., R.A.G., K.W. and J.R. were supported by NIH grant U54-HG006484-01. D.S. was supported by the Priority Program {\textquoteleft}Innate Sensing and Restriction of Retroviruses{\textquoteright} (SPP 1923) of the German Research Foundation (DFG). F.K. was funded by the Advanced ERC grant {\textquoteleft}Anti-Virome{\textquoteright} and the DFG-funded SFB 1279. G.W.C.T. and M.W.H. were supported by the Precision Health Initiative of Indiana University. B.H.H. was funded by NIH grant R37 AI050529. Comparative transcriptomics research was funded by NIH grant R24 OD010445. Publisher Copyright: {\textcopyright} 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",
year = "2018",
month = jan,
day = "3",
doi = "10.1038/nature25140",
language = "English (US)",
volume = "553",
pages = "77--81",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7686",
}