Cynomolgus macaque IL37 polymorphism and control of SIV infection

• Published in: Scientific reports 2019-05, Vol.9 (1), p.7981-7981, Article 7981
• Main Authors: Shiina, Takashi, Suzuki, Shingo, Congy-Jolivet, Nicolas, Aarnink, Alice, Garchon, Henri-Jean, Dereuddre-Bosquet, Nathalie, Vaslin, Bruno, Tchitchek, Nicolas, Desjardins, Delphine, Autran, Brigitte, Lambotte, Olivier, Theodorou, Ioannis, Le Grand, Roger, Blancher, Antoine
• Format: Article
• Language: English
• Subjects: 45; 45/47; 631/250/248; 692/699/255/1901; Animals; Base Sequence; Exons; Gene Expression; Gene polymorphism; Genes; Genetic Loci; Haplotypes; High-Throughput Nucleotide Sequencing; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - immunology; Humanities and Social Sciences; Immunology; Interferon-Stimulated Gene Factor 3, gamma Subunit - genetics; Interferon-Stimulated Gene Factor 3, gamma Subunit - immunology; Interleukin-1 - genetics; Interleukin-1 - immunology; Life Sciences; Linear Models; Macaca fascicularis; Male; multidisciplinary; Odds Ratio; Polymorphism, Single Nucleotide; Primates; Science; Science (multidisciplinary); Sequence Alignment; Simian Acquired Immunodeficiency Syndrome - genetics; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - pathology; Simian Immunodeficiency Virus - growth & development; Simian Immunodeficiency Virus - immunology; Simian Immunodeficiency Virus - pathogenicity; Single-nucleotide polymorphism; Viral Load - immunology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-44235-x

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.