Hantavirus‐induced immunity in rodent reservoirs and humans

Schönrich, Günther; Rang, Andreas; Lütteke, Nina; Raftery, Martin; Charbonnel, Nathalie; Ulrich, Rainer G.

doi:10.1111/j.1600-065x.2008.00694.x

Cited by 151 publications

(178 citation statements)

References 321 publications

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“…2013. 43: 2566-2576 Antigen processing 2567 available for prevention or treatment of human hantavirus infections [7,8].Hantaviruses are not directly cytopathic for infected cells, suggesting that the antiviral immune response itself causes hantavirus-associated syndromes [9,10]. In accordance, hantaviruses trigger an unusually potent reaction of CD8 + T lymphocytes, that is devoid of regulatory T cells, and still detectable years after resolution [11][12][13][14].…”

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Hantaviral mechanisms driving HLA class I antigen presentation require both RIG‐I and TRIF

et al. 2013

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Hantaviruses are emerging human pathogens. They induce an unusually strong antiviral response of human HLA class I (HLA-I) restricted CD8 + T cells that may contribute to tissue damage and hantavirus-associated disease. In this study, we analyzed possible hantaviral mechanisms that enhance the HLA-I antigen presentation machinery. Upon hantavirus infection of various human and primate cell lines, we observed transactivation of promoters controlling classical HLA molecules. Hantavirus-induced HLA-I upregulation required proteasomal activity and was associated with increased TAP expression. Intriguingly, human DCs acquired the capacity to cross-present antigen upon hantavirus infection. Furthermore, knockdown of TIR domain containing adaptor inducing IFN-β or retinoic acid inducible gene I abolished hantavirus-driven HLA-I induction. In contrast, MyD88-dependent viral sensors were not involved in HLA-I induction. Our results show that hantaviruses strongly boost the HLA-I antigen presentation machinery by mechanisms that are dependent on both retinoic acid inducible gene I and TIR domain containing adaptor inducing IFN-β.Keywords: Antigen presentation/processing · Cross-presentation/priming · Immunopathology · Infectious diseases · Innate immunity IntroductionRapidly changing ecosystems and climate facilitate the emergence of human infections with hantaviruses [1][2][3]. In Germany, increasing numbers of hantavirus-associated disease cases have been observed [4]. The enhanced health hazard emanating from pathogenic hantavirus species has been recognized by the German National Health Institute, which has recently reprioritized infecCorrespondence: Prof. Günther Schönrich e-mail: guenther.schoenrich@charite.de tious pathogens and placed hantaviruses in the highest priority group [5].Hantaviruses belong to the family Bunyaviridae and have segmented genomes [6]. The three viral RNA segments code for a nucleoprotein (N), two glycoproteins (Gn and Gc), and a RNA-dependent RNA polymerase. Hantaviruses are transmitted to humans by inhalation of virus-containing aerosols that are derived from the excreta of hantavirus-infected rodents. These natural reservoir hosts remain asymptomatic, although they are persistently infected. In striking contrast, hantaviruses are eliminated in humans at the cost of severe symptoms such as pulmonary or renal failure. Currently, no suitable vaccines or therapeutics are C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2013. 43: 2566-2576 Antigen processing 2567 available for prevention or treatment of human hantavirus infections [7,8].Hantaviruses are not directly cytopathic for infected cells, suggesting that the antiviral immune response itself causes hantavirus-associated syndromes [9,10]. In accordance, hantaviruses trigger an unusually potent reaction of CD8 + T lymphocytes, that is devoid of regulatory T cells, and still detectable years after resolution [11][12][13][14]. Human CD8 + T cells are stimulated by HLA class I (HLA-I) molecules that prese...

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Hantaviral mechanisms driving HLA class I antigen presentation require both RIG‐I and TRIF

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“…M. glareolus is the main specific reservoir of PUUV in the wild. Transmission between bank voles is exclusively horizontal and is mediated by the inhalation of infected aerosols or aggressive behavior (see a review in Schonrich et al, 2008). Infection with this virus is considered to be chronic (Meyer and Schmaljohn, 2000).…”

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

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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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“…Hastalığın akut dönemin-de virusun N proteinine karşı, geç döneminde ise G N ve G C proteinlerine karşı nötralizan antikorlar oluşur (19). Hastalı-ğın erken döneminde oluşan güçlü antikor yanıtı virus yayı-lımını önleyerek virusla infekte hücre sayısını azaltır.…”

Section: Patogenezunclassified

“…Hastalığın erken dönemin-de rölatif olarak yüksek düzeyde nötralizan antikor saptanan bireylerde hantavirus infeksiyonunun daha hafif seyrettiği gözlenmiştir. Hantavirusa karşı oluşan nötralizan antikorlar serumda yıllarca varlığını sürdürür ve kişiyi aynı virus tipine karşı reinfeksiyondan korur (19).…”

Section: Patogenezunclassified

Hantavirus Infections

Çelebi¹

2012

Klimik Dergisi

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ÖzetHantaviruslar, Bunyaviridae ailesinin Hantavirus cinsinde yer alan, kemirici (rodent) veya böcekçil (insektivor) kaynaklı, zarflı bir RNA virusu grubudur. Her hantavirus tipi o tipe özgü bir kemirici türü tarafından taşınır. Günümüze kadar 45 civarında hantavirus tipi saptanmış ve en az 20 tanesi insanlarda infeksiyon etkeni olarak gösterilmiştir. Hantaviruslar kemiricilerde çoğunlukla asemptomatik fakat kronik bir infeksiyona neden olur. Kemiriciler idrar ve dışkılarıyla aylarca çevreye virus saçar-lar. Amerika kıtasında bulunan hantavirus tipleri (Sin Nombre virusu, Andes virusu, Laguna Negra virusu, New York virusu vb.) hantavirus pulmoner sendromuna (HPS) neden olur ve oluşan infeksiyonun fatalitesi oldukça yüksektir (%30 civarında AbstractHantaviruses belonging to the Bunyaviridae family, and the genus Hantavirus, are a group of rodent-or insectivore-borne RNA viruses. Each Hantavirus type is carried by a specific rodent host species. Up to now, approximately 45 hantavirus types have been isolated and at least 20 have been identified as infectious agents in humans. Hantaviruses mostly cause asymptomatic but chronic infections in rodents. Rodents spread the viruses on the surfaces in the environment with their urine and feces during several months. Hantavirus types which exist in the Americas (Sin Nombre virus, Andes virus, Laguna Negra virus, New York virus etc.) cause Hantavirus pulmonary syndrome (HPS) and the fatality rate of the disease is quite high (around 30%). Hantavirus types which exist in Europe and Asia (Hantaan virus [HTNV], Seoul virus [SEOV], Dobrova virus [DOBV], Puumala virus [PUUV]) cause hemorrhagic fever with renal syndrome (HFRS). HTNV and SEOV in Asia, and PUUV and DOBV in Europe are the major agents of HFRS. Infection caused by HTNV or DOBV is a more serious disease with a fatality rate around 5-10%, while infection caused by PUUV is a mild disease with a fatality rate around 0.1%. Ribavirin was found to be effective in the treatment of HFRS in a few studies conducted in China and Korea. However, it was found to be ineffective in the treatment of HPS in America. The most effective method for prevention seems to be vaccination and studies are still ongoing for a safe and effective vaccine. The first human hantavirus outbreak in Turkey confirmed clinically and serologically was detected in the Zonguldak-Bartın region in February 2009. PUUV and DOBV were isolated from tissue samples of rodents captured in the outbreak region by using polymerase chain reaction and viral cell culture. Considering the current rodent and insectivore species in the country, in addition to PUUV and DOBV, the presence of Saaremaa virus, SEOV, Tula virus and Seewis virus may be anticipated in Turkey. Klimik Dergisi 2011; 24(3): 139-49.

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Hantavirus‐induced immunity in rodent reservoirs and humans

Cited by 151 publications

References 321 publications

Hantaviral mechanisms driving HLA class I antigen presentation require both RIG‐I and TRIF

Hantaviral mechanisms driving HLA class I antigen presentation require both RIG‐I and TRIF

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

Hantavirus Infections

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