MHC class I alleles influence set-point viral load and survival time in simian immunodeficiency virus-infected rhesus monkeys.
In HIV-infected humans and SIV-infected rhesus macaques, host genes influence viral containment and hence the duration of the disease-free latency period. Our knowledge of the rhesus monkey immunogenetics, however, is limited. In this study, we describe partial cDNA sequences of five newly discovered rhesus macaque (Mamu) class I alleles and PCR-based typing techniques for the novel and previously published Mhc class I alleles. Using 15 primer pairs for PCR-based typing and DNA sequence analysis, we identified at least 21 Mhc class I alleles in a cohort of 91 SIV-infected macaques. The results confirm the presence of multiple class I genes in rhesus macaques. Of these alleles, Mamu-A*01 was significantly associated with lower set-point viral load and prolonged survival time. Mamu-A*1303 was associated with longer survival and a "novel" Mhc class I allele with lower set-point viral load. The alleles are frequent in rhesus macaques of Indian origin (12-22%). In addition, survival probability of individual SIV-infected rhesus monkeys increased with their number of alleles considered to be associated with longer survival. The results contribute to improve the interpretation and quality of preclinical studies in rhesus monkeys.
Mühl
Thorsten
T
Department of Virology and Immunology, German Primate Center, Goettingen, Germany.
Krawczak
Michael
M
Ten Haaft
Peter
P
Hunsmann
Gerhard
G
Sauermann
Ulrike
U
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005787:Gene Frequency / Q000276:immunology; D005805:Genes, MHC Class I / Q000502:physiology*; D008040:Genetic Linkage / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006650:Histocompatibility Testing / Q000379:methods; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000401:mortality* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D015996:Survival Rate; D019562:Viral Load
D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D010446:Peptide Fragments