Natural host genetic resistance to lentiviral CNS sisease: A neuroprotective MHC class I allele in SIV-infected macaques

Joseph L. Mankowski, Suzanne E. Queen, Caroline S. Fernandez, Patrick M. Tarwater, Jami M. Karper, Robert J. Adams, Stephen J. Kent

Research output: Contribution to journalArticle

Abstract

Human immunodeficiency virus (HIV) infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS) have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS) disease using a well-characterized simian immunodeficiency (SIV)/ pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis) was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5). Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P,0.001). Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

Original languageEnglish (US)
Article numbere3603
JournalPloS one
Volume3
Issue number11
DOIs
StatePublished - Nov 3 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Natural host genetic resistance to lentiviral CNS sisease: A neuroprotective MHC class I allele in SIV-infected macaques'. Together they form a unique fingerprint.

  • Cite this