Influence of the MHC genotype on the progression of experimental SIV infection in the Mauritian cynomolgus macaque
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Experimental infection of Mauritian cynomolgus macaques by simian immunodeficiency virus is a representative model of HIV infection, currently in favour for evaluating the efficacy of new preventive or curative treatments. Extensive studies of major histocompatibility complex (MHC) polymorphism by microsatellites revealed seven haplotypes (H1–H7). We present statistical evidence of the influence of MHC polymorphism on the set-point plasma viral load (PVL). Our analysis was based on the study of 45 Mauritian cynomolgus macaques inoculated by intravenous or intrarectal injection of a 50 AID50 dose of the SIVmac251 virus. The animals received no treatment before or after the inoculation. MHC polymorphism was investigated by means of 20 microsatellites distributed across the MHC and by DRB genotyping using the DGGE sequencing method. Statistical analysis with Unphased software revealed that two markers located in the class IB region significantly influenced the Log PVL and that three class IB haplotypes were significantly associated with lower (H2 or H6) or higher (H4) set-point Log PVL values. Although the impact of MHC on Log PVL was found to be low (around one Log10), it is important to dispose of animals paired for their MHC genotypes, each animal tested for a given treatment and its untreated control, to minimize the influence of the MHC and clearly reveal the effect of the treatment.
KeywordsSIVmac251 MHC Microsatellites Macaca fascicularis
We are pleased to thank Béatrice Atlan, Audrey Dauba, Stéphanie Despiau-Schiavinato and Sylvie Hébrard, Benoit Delache and Patricia Brochard for their excellent technical assistance. We thank Takashi Shiina for the location of the markers on the cynomolgus MHC map. We thank also Christophe Joubert and the animal facility staff of the CEA. We thank the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS) for its financial support.
Conflict of interest
The authors declare that they have no conflict of interest.
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