Cynomolgus macaque IL37 polymorphism and control of SIV infection

Takashi Shiina (1) , Shingo Suzuki (1) , Nicolas Congy-Jolivet (2, 3) , Alice Aarnink (2) , Henri-Jean Garchon (4, 5) , Nathalie Dereuddre-Bosquet (6, 7) , Bruno Vaslin (6, 7) , Nicolas Tchitchek (7, 6) , Delphine Desjardins (6, 7) , Brigitte Autran (8, 9) , Olivier Lambotte (6, 7, 10) , Ioannis Theodorou (8) , Roger Le Grand (7, 6) , Antoine Blancher (11, 2, 3)

1 Tokai University
2 LIMT - Laboratoire d'Immunogénétique Moléculaire
3 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
4 Hôpital Ambroise Paré [AP-HP]
5 IRIS - Inflammation rhumatismale et système immunitaire
6 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
7 IDMIT - Infectious Diseases Models for Innovative Therapies
8 CIMI - Centre d'Immunologie et des Maladies Infectieuses
9 CHU Pitié-Salpêtrière [AP-HP]
10 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
11 CPTP - Centre de Physiopathologie Toulouse Purpan

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.

Domaines: Sciences du Vivant [q-bio]; Immunologie

Takashi Shiina, Shingo Suzuki, Nicolas Congy-Jolivet, Alice Aarnink, Henri-Jean Garchon, et al.. Cynomolgus macaque IL37 polymorphism and control of SIV infection. Scientific Reports, 2019, 9 (1), pp.7981. ⟨10.1038/s41598-019-44235-x⟩. ⟨hal-02149363⟩