Publication

Progression to AIDS in SIV-infected rhesus macaques is associated with distinct KIR and MHC class 1 polymorphisms and NK cell dysfunction

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Last modified
  • 02/20/2025
Type of Material
Authors
    Christina Albrecht, Leibniz-Institute for Primate ResearchDorthe Malzahn, University of GottingenMarkus Brameier, Leibniz-Institute for Primate ResearchMeike Hermes, Leibniz-Institute for Primate ResearchAftab Ansari, Emory UniversityLutz Walter, Leibniz-Institute for Primate Research
Language
  • English
Date
  • 2014-11-28
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2014 Albrecht, Malzahn, Brameier, Hermes, Ansari and Walter.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1664-3224
Volume
  • 5
Issue
  • NOV
Start Page
  • 600
End Page
  • 600
Supplemental Material (URL)
Abstract
  • Killer cell immunoglobulin-like receptors (KIR) regulate the activity of natural killer (NK) cells and have been shown to be associated with susceptibility to a number of human infectious diseases. Here, we analyzed NK cell function and genetic associations in a cohort of 52 rhesus macaques experimentally infected with SIVmac and subsequently stratified into high viral load (HVL) and low viral load (LVL) plasma viral loads at set point. This stratification coincided with fast (HVL) and slow (LVL) disease progression indicated by the disease course and critical clinical parameters including CD4+ T cell counts. HVL animals revealed sustained proliferation of NK cells but distinct loss of peripheral blood NK cell numbers and lytic function. Genetic analyses revealed that KIR genes 3DL05, 3DS05, and 3DL10 as well as 3DSW08, 3DLW03, and 3DSW09 are correlated, most likely due to underlying haplotypes. SIV-infection outcome associated with presence of transcripts for two inhibitory KIR genes (KIR3DL02, KIR3DL10) and three activating KIR genes (KIR3DSW08, KIR3DS02, KIR3DS05). Presence of KIR3DL02 and KIR3DSW08 was associated with LVL outcome, whereas presence of KIR3DS02 was associated with HVL outcome. Furthermore, we identified epistasis between KIR and MHC class I alleles as the transcript presence of the correlated genes KIR3DL05, KIR3DS05, and KIR3DL10 increased HVL risk when Mamu-B*012 transcripts were also present or when Mamu-A1*001 transcripts were absent. These genetic associations were mirrored by changes in the numbers, the level of proliferation, and lytic capabilities of NK cells as well as overall survival time and gastro-intestinal tissue viral load.
Author Notes
  • Correspondence: Lutz Walter, German Primate Center, Leibniz-Institute for Primate Research, Kellnerweg 4, Göttingen 37077, Germany e-mail: walter@dpz.eu
Keywords
Research Categories
  • Health Sciences, Epidemiology
  • Health Sciences, Immunology

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