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Viruses 2014, 6(5), 2214-2241;

Immunogenetic Factors Affecting Susceptibility of Humans and Rodents to Hantaviruses and the Clinical Course of Hantaviral Disease in Humans

INRA, UMR CBGP (INRA/IRD/Cirad/Montpellier SupAgro), Campus international de Baillarguet, CS 30016, Montferrier-sur-Lez F-34988, France
Laboratoire de génétique des microorganismes, Université de Liège, Liège 4000, Belgium
Department of Virology, Haartman Institute, University of Helsinki, POB 21, FI-00014 Helsinki, Finland
Finnish Forest Research Institute, POB 18, FI-01301 Vantaa, Finland
Department of Virology and Immunology, HUSLAB, Helsinki University Central Hospital, FI-00014 Helsinki, Finland
Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, FI-00014 Helsinki, Finland
School of Medicine, University of Tampere, FI-33521 Tampere, Finland
Department of Internal Medicine, Tampere University Hospital, FI-33521 Tampere, Finland
Author to whom correspondence should be addressed.
Received: 29 November 2013 / Revised: 17 March 2014 / Accepted: 16 May 2014 / Published: 26 May 2014
(This article belongs to the Special Issue Hantaviruses)
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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. View Full-Text
Keywords: hantavirus; Puumala virus; interaction; hosts; reservoirs; rodents; immunity-related genes hantavirus; Puumala virus; interaction; hosts; reservoirs; rodents; immunity-related genes

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Charbonnel, N.; Pagès, M.; Sironen, T.; Henttonen, H.; Vapalahti, O.; Mustonen, J.; Vaheri, A. Immunogenetic Factors Affecting Susceptibility of Humans and Rodents to Hantaviruses and the Clinical Course of Hantaviral Disease in Humans. Viruses 2014, 6, 2214-2241.

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