Switch to high-level virus replication and HLA class I upregulation in differentiating megakaryocytic cells after infection with pathogenic hantavirus

Lütteke, Nina; Raftery, Martin; Lalwani, Pritesh; Lee, Min-Hi; Giese, Thomas; Voigt, Sebastian; Bannert, Norbert; Schulze, Harald; Krüger, Detlev H.; Schönrich, Günther

doi:10.1016/j.virol.2010.05.028

Cited by 36 publications

(36 citation statements)

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“…Subsequently, cells were centrifuged at 600g for 5 min at 4 • C and resuspended in FACS wash buffer (PBS pH 7.4, 0.1% FCS) to rehydrate for 15-30 min. Cells were then stained with standard FACS staining procedure as described previously [46]. A549 cells treated with 2000-5000 IU/mL IFN-α (ImmunoTools) for 24 h served as a positive control for staining of human HLA-I molecules in all assays unless otherwise specified.…”

Section: Flow Cytometrymentioning

confidence: 99%

“…LightCycler qRT-PCR was performed essentially as previously described [46]. Briefly, cells were lysed with MagNA Pure lysis buffer (Roche) and mRNA was isolated with a MagNA Pure-LC device using standard protocols.…”

Section: Qrt-pcrmentioning

confidence: 99%

“…Cell surface staining for antigens was performed as described previously [46]. For staining of human HLA-I molecules, a mAb (clone W6/32) was used that reacts with a monomorphic epitope of the heavy chain bound to β2m constituting the classical human HLA-I molecules (HLA-A, -B, -C).…”

Section: Flow Cytometrymentioning

confidence: 99%

“…Immunofluorescence analysis was performed as described previously [46]. For staining of HTNV N protein, a cross-reactive serum from pig immunized with N protein from Dobrava/Belgrade virus followed by FITC-conjugated goat-anti-pig (Dianova) as a secondary reagent was used.…”

Section: Immunofluorescence Analysismentioning

confidence: 99%

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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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Section: Flow Cytometrymentioning

confidence: 99%

Section: Qrt-pcrmentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

Section: Immunofluorescence Analysismentioning

confidence: 99%

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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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“…Hemorrhagic fever viruses not only interact with platelets, but can also infect megakaryocytes. This is the case for some strains of Hantavirus associated with hemorrhagic fever, where megakaryocyte infection is thought to induce their destruction by T-cells [139]. Similarly, cytomegalovirus infection of megakaryocytes triggers caspase-mediated apoptosis resulting in thrombocytopenia [140].…”

Section: Platelet Activation By Indirect Interactions With Microbesmentioning

confidence: 99%

The Role of Platelets in Viral Hemorrhagic Fevers

Cox¹,

Salvato²,

Zapata³

2012

J Bioterror Biodef

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Review: Viral infections and mechanisms of thrombosis and bleeding

Goeijenbier

Wissen

Weg

et al. 2012

Journal of Medical Virology

264

267

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Viral infections are associated with coagulation disorders. All aspects of the coagulation cascade, primary hemostasis, coagulation, and fibrinolysis, can be affected. As a consequence, thrombosis and disseminated intravascular coagulation, hemorrhage, or both, may occur. Investigation of coagulation disorders as a consequence of different viral infections have not been performed uniformly. Common pathways are therefore not fully elucidated. In many severe viral infections there is no treatment other than supportive measures. A better understanding of the pathophysiology behind the association of viral infections and coagulation disorders is crucial for developing therapeutic strategies. This is of special importance in case of severe complications, such as those seen in hemorrhagic viral infections, the incidence of which is increasing worldwide. To date, only a few promising targets have been discovered, meaning the implementation in a clinical context is still hampered. This review discusses non-hemorrhagic and hemorrhagic viruses for which sufficient data on the association with hemostasis and related clinical features is available. This will enable clinicians to interpret research data and place them into a perspective.

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Switch to high-level virus replication and HLA class I upregulation in differentiating megakaryocytic cells after infection with pathogenic hantavirus

Cited by 36 publications

References 59 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

The Role of Platelets in Viral Hemorrhagic Fevers

Review: Viral infections and mechanisms of thrombosis and bleeding

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