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

Nature. 2018 Jan 3;553(7686):77-81. doi: 10.1038/nature25140.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / genetics*
  • Acquired Immunodeficiency Syndrome / virology
  • Amino Acid Sequence
  • Animals
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cercocebus atys / genetics*
  • Cercocebus atys / immunology
  • Cercocebus atys / virology*
  • Exons / genetics
  • Female
  • Frameshift Mutation / genetics
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Genome / genetics*
  • Genomics
  • HIV / pathogenicity
  • Host Specificity / genetics*
  • Humans
  • Macaca / virology
  • Sequence Deletion
  • Simian Acquired Immunodeficiency Syndrome / genetics
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus* / pathogenicity
  • Species Specificity
  • Toll-Like Receptor 4 / chemistry
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology
  • Transcriptome / genetics
  • Whole Genome Sequencing

Substances

  • Cell Adhesion Molecules
  • Toll-Like Receptor 4