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

Viruses

Nathalie Charbonnel⁴  Marie Pagès⁴  Tarja Sironen²  Heikki Henttonen³  Olli Vapalahti²  Jukka Mustonen¹ 

[1] School of Medicine, University of Tampere, FI-33521 Tampere, Finland; E-Mail:;Department of Virology, Haartman Institute, University of Helsinki, POB 21, FI-00014 Helsinki, Finland; E-Mails:;Finnish Forest Research Institute, POB 18, FI-01301 Vantaa, Finland; E-Mail:;INRA, UMR CBGP (INRA/IRD/Cirad/Montpellier SupAgro), Campus international de Baillarguet, CS 30016, Montferrier-sur-Lez F-34988, France; E-Mail:

关键词: hantavirus;    Puumala virus;    interaction;    hosts;    reservoirs;    rodents;    immunity-related genes;   

DOI  :  10.3390/v6052214

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.