Immunogenetic factors affecting susceptibility of humans and rodents to hantaviruses and the clinical course of hantaviral disease in humans.

Nathalie Charbonnel (1) , Marie Pagès (1, 2) , Tarja Sironen (3) , Heikki Henttonen (4) , Olli Vapalahti (3, 5, 6) , Jukka Mustonen (7, 8) , Antti Vaheri (3, 5)

1 UMR CBGP - Centre de Biologie pour la Gestion des Populations
2 Laboratoire de génétique des microorganismes
3 Department of Virology [Helsinki]
4 Finnish Forest Research Institute
5 Department of Virology and Immunology
6 Department of Veterinary Biosciences, Faculty of Veterinary Medicine
7 School of Medicine
8 Department of Internal Medicine

We reviewed the associations of immunity-related genes with susceptibility of humans and rodents to hantaviruses, and with severity of hantaviral diseases in humans. Several class I and class II HLA haplotypes were linked with severe or benign hantavirus infections, and these haplotypes varied among localities and hantaviruses. The polymorphism of other immunity-related genes including the C4A gene and a high-producing genotype of TNF gene associated with severe PUUV infection. Additional genes that may contribute to disease or to PUUV infection severity include non-carriage of the interleukin-1 receptor antagonist (IL-1RA) allele 2 and IL-1β (-511) allele 2, polymorphisms of plasminogen activator inhibitor (PAI-1) and platelet GP1a. In addition, immunogenetic studies have been conducted to identify mechanisms that could be linked with the persistence/clearance of hantaviruses in reservoirs. Persistence was associated during experimental infections with an upregulation of anti-inflammatory responses. Using natural rodent population samples, polymorphisms and/or expression levels of several genes have been analyzed. These genes were selected based on the literature of rodent or human/hantavirus interactions (some Mhc class II genes, Tnf promoter, and genes encoding the proteins TLR4, TLR7, Mx2 and β3 integrin). The comparison of genetic differentiation estimated between bank vole populations sampled over Europe, at neutral and candidate genes, has allowed to evidence signatures of selection for Tnf, Mx2 and the Drb Mhc class II genes. Altogether, these results corroborated the hypothesis of an evolution of tolerance strategies in rodents. We finally discuss the importance of these results from the medical and epidemiological perspectives.

Domaines: Sciences agricoles; Biologie animale; Biologie du développement; Immunité adaptative; Santé publique et épidémiologie

Nathalie Charbonnel, Marie Pagès, Tarja Sironen, Heikki Henttonen, Olli Vapalahti, et al.. Immunogenetic factors affecting susceptibility of humans and rodents to hantaviruses and the clinical course of hantaviral disease in humans.. Viruses, 2014, 6 (5), pp.2214-41. ⟨10.3390/v6052214⟩. ⟨hal-01190031⟩