Associations between MHC genes and Puumala virus infection in Myodes glareolus are detected in wild populations, but not from experimental infection data

Guivier, Emmanuel; Galan, Maxime; Malé, Pierre‐Jean G.; Kallio, Eva R.; Voutilainen, Liina; Henttonen, Heikki; Olsson, Gert E.; Lundkvist, Åke; Tersago, Katrien; Augot, Denis; Cosson, Jean‐François; Charbonnel, Nathalie

doi:10.1099/vir.0.021600-0

Cited by 24 publications

(22 citation statements)

References 35 publications

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“…Nevertheless, besides the deprived immune response in wild compared to laboratory-reared animals, other factors may also explain the lesser propagation of hantavirus in laboratory studies: the impaired infectivity of cell-adapted hantavirus for the natural host (Lundkvist et al, 1997), higher than natural infecting doses (Hardestam et al, 2008) and the low immunogenetic variability in colonized experimental animals (Guivier et al, 2010a) may all bias the shedding patterns observed in infection trials.…”

Section: Discussionmentioning

confidence: 99%

Life-long shedding of Puumala hantavirus in wild bank voles (Myodes glareolus)

Voutilainen

Sironen

Tonteri

et al. 2015

Journal of General Virology

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The knowledge of viral shedding patterns and viraemia in the reservoir host species is a key factor in assessing the human risk of zoonotic viruses. The shedding of hantaviruses (family Bunyaviridae) by their host rodents has widely been studied experimentally, but rarely in natural settings. Here we present the dynamics of Puumala hantavirus (PUUV) shedding and viraemia in naturally infected wild bank voles (Myodes glareolus). In a monthly capture-mark-recapture study, we analysed 18 bank voles for the presence and relative quantity of PUUV RNA in the excreta and blood from 2 months before up to 8 months after seroconversion. The proportion of animals shedding PUUV RNA in saliva, urine and faeces peaked during the first month after seroconversion, but continued throughout the study period with only a slight decline. The quantity of shed PUUV in reverse transcription quantitative PCR (RT-qPCR) positive excreta was constant over time. In blood, PUUV RNA was present for up to 7 months but both the probability of viraemia and the virus load declined with time. Our findings contradict the current view of a decline in virus shedding after the acute phase and a short viraemic period in hantavirus infection -an assumption widely adopted in current epidemiological models. We suggest the life-long shedding as a means of hantaviruses to survive over host population bottlenecks, and to disperse in fragmented habitats where local host and/or virus populations face temporary extinctions. Our results indicate that the kinetics of pathogens in wild hosts may differ considerably from those observed in laboratory settings.

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Section: Discussionmentioning

confidence: 99%

Life-long shedding of Puumala hantavirus in wild bank voles (Myodes glareolus)

Voutilainen

Sironen

Tonteri

et al. 2015

Journal of General Virology

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“…They showed that infection outcomes were highly variable among recipient voles, independently of sex or age. Guivier et al [94] evaluated whether immunity-related gene polymorphism could explain these differences. Unfortunately, no significant associations could be detected between infection success and immunity-related gene polymorphism of these bank voles.…”

Section: Impact Of Immunity-related Genes On the Risk Of Hantavirumentioning

confidence: 99%

“…The relative risk associated with Mygl-Drb*117 was high (RR = 4.82, p = 0.062) although not significant. This absence of relationship was likely to be explained by the loss of genetic variability that occurred during the long-term multigenerational captivity of these rodents [94]. …”

Section: Impact Of Immunity-related Genes On the Risk Of Hantavirumentioning

confidence: 99%

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

Charbonnel

Pagès

Sironen

et al. 2014

Viruses

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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.

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“…Field surveys and laboratory experiments have indicated that the probability of infection with PUUV differs between individual bank voles, which also differ in their response to PUUV infection (Olsson et al, 2002;Hardestam et al, 2008;Deter et al, 2008b;Guivier et al, 2010a). Polymorphism and variability in the expression of immune genes may determine the ability of the vole to control hantavirus replication (Plyusnin et al, 1997;Makela et al, 2002;Klein et al, 2004;Terajima et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Landscape features and helminth co-infection shape bank vole immunoheterogeneity, with consequences for Puumala virus epidemiology

et al. 2013

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Heterogeneity in environmental conditions helps to maintain genetic and phenotypic diversity in ecosystems. As such, it may explain why the capacity of animals to mount immune responses is highly variable. The quality of habitat patches, in terms of resources, parasitism, predation and habitat fragmentation may, for example, trigger trade-offs ultimately affecting the investment of individuals in various immunological pathways. We described spatial immunoheterogeneity in bank vole populations with respect to landscape features and co-infection. We focused on the consequences of this heterogeneity for the risk of Puumala hantavirus (PUUV) infection. We assessed the expression of the Tnf-a and Mx2 genes and demonstrated a negative correlation between PUUV load and the expression of these immune genes in bank voles. Habitat heterogeneity was partly associated with differences in the expression of these genes. Levels of Mx2 were lower in large forests than in fragmented forests, possibly due to differences in parasite communities. We previously highlighted the positive association between infection with Heligmosomum mixtum and infection with PUUV. We found that Tnf-a was more strongly expressed in voles infected with PUUV than in uninfected voles or in voles co-infected with the nematode H. mixtum and PUUV. H. mixtum may limit the capacity of the vole to develop proinflammatory responses. This effect may increase the risk of PUUV infection and replication in host cells. Overall, our results suggest that close interactions between landscape features, co-infection and immune gene expression may shape PUUV epidemiology.

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Associations between MHC genes and Puumala virus infection in Myodes glareolus are detected in wild populations, but not from experimental infection data

Cited by 24 publications

References 35 publications

Life-long shedding of Puumala hantavirus in wild bank voles (Myodes glareolus)

Life-long shedding of Puumala hantavirus in wild bank voles (Myodes glareolus)

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

Landscape features and helminth co-infection shape bank vole immunoheterogeneity, with consequences for Puumala virus epidemiology

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