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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)77-81
Number of pages5
JournalNature
Volume553
Issue number7686
DOIs
StatePublished - Jan 3 2018

Fingerprint

Cercocebus atys
Simian Immunodeficiency Virus
Acquired Immunodeficiency Syndrome
Genome
Macaca
Cell Adhesion Molecules
HIV
Toll-Like Receptor 4
Viremia
Virus Diseases
Genes
Exons
Ligands

ASJC Scopus subject areas

  • General

Cite this

Palesch, D., Bosinger, S. E., Tharp, G. K., Vanderford, T. H., Paiardini, M., Chahroudi, A., ... Silvestri, G. (2018). Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host. Nature, 553(7686), 77-81. https://doi.org/10.1038/nature25140

Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host. / Palesch, David; Bosinger, Steven E.; Tharp, Gregory K.; Vanderford, Thomas H.; Paiardini, Mirko; Chahroudi, Ann; Johnson, Zachary P.; Kirchhoff, Frank; Hahn, Beatrice H.; Norgren, Robert B; Patel, Nirav B.; Sodora, Donald L.; Dawoud, Reem A.; Stewart, Caro Beth; Seepo, Sara M.; Harris, R. Alan; Liu, Yue; Raveendran, Muthuswamy; Han, Yi; English, Adam; Thomas, Gregg W.C.; Hahn, Matthew W.; Pipes, Lenore; Mason, Christopher E.; Muzny, Donna M.; Gibbs, Richard A.; Sauter, Daniel; Worley, Kim; Rogers, Jeffrey; Silvestri, Guido.

In: Nature, Vol. 553, No. 7686, 03.01.2018, p. 77-81.

Research output: Contribution to journalArticle

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, CB, Seepo, SM, Harris, RA, 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 2018, 'Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host', Nature, vol. 553, no. 7686, pp. 77-81. https://doi.org/10.1038/nature25140
Palesch D, Bosinger SE, Tharp GK, Vanderford TH, Paiardini M, Chahroudi A et al. Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host. Nature. 2018 Jan 3;553(7686):77-81. https://doi.org/10.1038/nature25140
Palesch, David ; Bosinger, Steven E. ; Tharp, Gregory K. ; Vanderford, Thomas H. ; Paiardini, Mirko ; Chahroudi, Ann ; Johnson, Zachary P. ; Kirchhoff, Frank ; Hahn, Beatrice H. ; Norgren, Robert B ; Patel, Nirav B. ; Sodora, Donald L. ; Dawoud, Reem A. ; Stewart, Caro Beth ; Seepo, Sara M. ; Harris, R. Alan ; Liu, Yue ; Raveendran, Muthuswamy ; Han, Yi ; English, Adam ; Thomas, Gregg W.C. ; Hahn, Matthew W. ; Pipes, Lenore ; Mason, Christopher E. ; Muzny, Donna M. ; Gibbs, Richard A. ; Sauter, Daniel ; Worley, Kim ; Rogers, Jeffrey ; Silvestri, Guido. / Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host. In: Nature. 2018 ; Vol. 553, No. 7686. pp. 77-81.
@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",
year = "2018",
month = "1",
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",

}

TY - JOUR

T1 - Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host

AU - Palesch, David

AU - Bosinger, Steven E.

AU - Tharp, Gregory K.

AU - Vanderford, Thomas H.

AU - Paiardini, Mirko

AU - Chahroudi, Ann

AU - Johnson, Zachary P.

AU - Kirchhoff, Frank

AU - Hahn, Beatrice H.

AU - Norgren, Robert B

AU - Patel, Nirav B.

AU - Sodora, Donald L.

AU - Dawoud, Reem A.

AU - Stewart, Caro Beth

AU - Seepo, Sara M.

AU - Harris, R. Alan

AU - Liu, Yue

AU - Raveendran, Muthuswamy

AU - Han, Yi

AU - English, Adam

AU - Thomas, Gregg W.C.

AU - Hahn, Matthew W.

AU - Pipes, Lenore

AU - Mason, Christopher E.

AU - Muzny, Donna M.

AU - Gibbs, Richard A.

AU - Sauter, Daniel

AU - Worley, Kim

AU - Rogers, Jeffrey

AU - Silvestri, Guido

PY - 2018/1/3

Y1 - 2018/1/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85040181025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040181025&partnerID=8YFLogxK

U2 - 10.1038/nature25140

DO - 10.1038/nature25140

M3 - Article

C2 - 29300007

AN - SCOPUS:85040181025

VL - 553

SP - 77

EP - 81

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7686

ER -