Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques.
In both human immunodeficiency virus-infected humans and simian immunodeficiency virus (SIV)-infected macaques, genes encoded in the major histocompatibility complex (MHC) class I region are important determinants of disease progression. However, compared to the human human lymphocyte antigen complex, the macaque MHC region encodes many more class I genes. Macaques with the same immunodominant class I genes express additional Mhc genes with the potential to influence the disease course. We therefore assessed the association between of the Mhc class I haplotypes, rather than single gene variants, and survival time in SIV-infected rhesus macaques (Macaca mulatta). DNA sequence analysis and Mhc genotyping of 245 pedigreed monkeys identified 17 Mhc class I haplotypes that constitute 10 major genotypes. Among 81 vaccination-naive, SIV-infected macaques, 71 monkeys carried at least one Mhc class I haplotype encoding only MHC antigens that were incapable of inducing an effective anti-SIV cytotoxic T lymphocytes response. Study of these macaques enabled us to relate individual Mhc class I haplotypes to slow, medium and rapid disease progression. In a post hoc analysis, classification according to disease progression was found to explain at least 48% of the observed variation of survival time.
Sauermann
U
U
Department of Virology and Immunology, German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany. usauerm@dpz.eu
Siddiqui
R
R
Suh
Y-S
YS
Platzer
M
M
Leuchte
N
N
Meyer
H
H
Mätz-Rensing
K
K
Stoiber
H
H
Nürnberg
P
P
Hunsmann
G
G
Stahl-Hennig
C
C
Krawczak
M
M
D000483:Alleles; D000818:Animals; D015331:Cohort Studies; D018450:Disease Progression; D005787:Gene Frequency; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013223:Statistics as Topic; D016019:Survival Analysis
D015395:Histocompatibility Antigens Class I