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 Tarwater, Jami M. Karper, Robert John 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

Fingerprint

genetic resistance
Macaca
Neurology
central nervous system
Central Nervous System
Alleles
alleles
central nervous system diseases
Animals
Central Nervous System Diseases
nervous system diseases
animals
viral load
Nervous System Diseases
Viral Load
Viruses
HIV
Macaca nemestrina
acquired immunodeficiency syndrome
immunosuppression

ASJC Scopus subject areas

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

Cite this

Natural host genetic resistance to lentiviral CNS sisease : A neuroprotective MHC class I allele in SIV-infected macaques. / Mankowski, Joseph L; Queen, Suzanne E.; Fernandez, Caroline S.; Tarwater, Patrick; Karper, Jami M.; Adams, Robert John; Kent, Stephen J.

In: PLoS One, Vol. 3, No. 11, e3603, 03.11.2008.

Research output: Contribution to journalArticle

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