Abstract

The association between gene polymorphisms and plasma virus load at the set point (SP-PVL) was investigated in Mauritian macaques inoculated with SIV. Among 44 macaques inoculated with 50 AID50, six individuals were selected: three with SP-PVL among the highest and three with SP-PVL among the lowest. The exons of 390 candidate genes of these six animals were sequenced. Twelve non-synonymous single nucleotide polymorphisms (NS-SNPs) lying in nine genes potentially associated with PVL were genotyped in 23 animals. Three NS-SNPs with probabilities of association with PVL less than 0.05 were genotyped in a total of 44 animals. One NS-SNP lying in exon 1 of the IL37 gene displayed a significant association (p = 3.33 × 10−4) and a strong odds ratio (19.52). Multiple linear regression modeling revealed three significant predictors of SP-PVL, including the IL37 exon 1 NS-SNP (p = 0.0004) and the MHC Class IB haplotypes M2 (p = 0.0007) and M6 (p = 0.0013). These three factors in conjunction explained 48% of the PVL variance (p = 4.8 × 10−6). The potential role of IL37 in the control of SIV infection is discussed.

Highlights

  • Among the Old World monkeys used as animal models of SIV infection, the cynomolgus macaque (Macaca fascicularis, hereinafter abbreviated as Mafa), which is easy to breed in captivity, is increasingly being used[1]

  • We explored the association between SIV plasma viral load at the set point (SP-Plasma viral load (PVL)) and polymorphism in the coding regions of 390 candidate genes involved in the progression of viral replication or the immune defense against infection

  • By comparing SP-PVL data generated from the six animals, 12 NS-single nucleotide polymorphisms (SNPs) located on nine genes were associated with the PVL values

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Summary

Introduction

Among the Old World monkeys used as animal models of SIV infection, the cynomolgus macaque (Macaca fascicularis, hereinafter abbreviated as Mafa), which is easy to breed in captivity, is increasingly being used[1]. Ericsen et al.[14] identified candidate loci associated to the control of SIV infection, by whole genome sequencing of twelve Mauritian cynomolgus macaques that exhibited highly differing SP-PVL. We explored the association between SIV plasma viral load at the set point (SP-PVL) and polymorphism in the coding regions of 390 candidate genes involved in the progression of viral replication or the immune defense against infection. The polymorphism of these genes was characterized by targeted resequencing of DNA fragments encompassing all exons of the selected candidate genes. We discussed the potential impact of IL37 polymorphism in the control of SIV infection in cynomolgus macaques

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