Increased permeability of human endothelial cell line EA.hy926 induced by hantavirus-specific cytotoxic T lymphocytes

Hayasaka, Daisuke; Maeda, Ken; Ennis, Francis A.; Terajima, Masanori

doi:10.1016/j.virusres.2006.08.006

Cited by 56 publications

(44 citation statements)

References 49 publications

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“…Multiple mechanisms have been proposed to account for the vascular leakage caused by hantaviruses, including, predominantly, T cell-mediated immunopathology (4,17,39,76,79). Consistent with this, SNV-specific T cells induce permeability of human endothelial cells expressing SNV antigens in vitro (29). In humans, large numbers of T cells and cytokine-producing cells have been reported in the lungs, spleens, and hearts of HPS patients (52,57,88), and T cell numbers have been suggested to correlate with disease severity (39).…”

mentioning

confidence: 68%

“…The small sample size and the discontinuity in T cell numbers as disease severity increases also limit the strength of this correlation. Moreover, in vitro evidence that CD8 ϩ T cells obtained from an HFRS patient are able to specifically lyse endothelial cells expressing an SNV-derived peptide (29) does not accurately reflect the lack of endothelial cell apoptosis during human HPS. Since effector CD8 ϩ and CD4 ϩ T cells can secrete many of the same vasoactive cytokines, the CD4 ϩ subset in hamsters may be more likely to mediate pathogenesis in hamsters since it is more prevalent.…”

Section: Vol 85 2011 T Cells Are Not Required For Hps Pathogenesis mentioning

confidence: 99%

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T Cells Are Not Required for Pathogenesis in the Syrian Hamster Model of Hantavirus Pulmonary Syndrome

Hammerbeck

Hooper

2011

J Virol

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Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). In hamsters, ANDV causes a respiratory distress syndrome closely resembling human HPS. The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, T cell immunopathology has been implicated on the basis of circumstantial and corollary evidence. Here, we show that following ANDV challenge, hamster T cell activation corresponds with the onset of disease. However, treatment with cyclophosphamide or specific T cell depletion does not impact the course of disease or alter the number of surviving animals, despite significant reductions in T cell number. These data demonstrate, for the first time, that T cells are not required for hantavirus pathogenesis in the hamster model of human HPS. Depletion of T cells from Syrian hamsters did not significantly influence early events in disease progression. Moreover, these data argue for a mechanism of hantavirus-induced vascular permeability that does not involve T cell immunopathology.

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confidence: 68%

Section: Vol 85 2011 T Cells Are Not Required For Hps Pathogenesis mentioning

confidence: 99%

T Cells Are Not Required for Pathogenesis in the Syrian Hamster Model of Hantavirus Pulmonary Syndrome

Hammerbeck

Hooper

2011

J Virol

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“…Suggestions for causes of hantavirus permeability are abundant, and T cells and TNF-␣ have been suggested to be involved in hantavirus-associated disease (35,76). Primed cytotoxic T lymphocytes kill infected endothelial cells in vitro, which has been suggested as a mechanism of capillary permeability (23). However, the endothelium of HPS patients is not damaged, and cytotoxic-T-lymphocyte-directed lysis of endothelial cells would likely result in hemorrhagic disease rather than the transudative pulmonary edema observed during HPS (8,76).…”

Section: Vol 82 2008 Hantaviruses Direct Endothelial Cell Permeabilmentioning

confidence: 99%

“…T cells, tumor necrosis factor alpha (TNF-␣), and cytokines have been suggested to be involved in permeability, but their contribution to HFRS or HPS diseases remains a question (23,35,76). A prominent link between vascular permeability disorders and hantavirus disease stems from the role of ␤3 integrins in hemorrhagic disease and the use and dysregulation of ␤3 integrin function by pathogenic hantaviruses (3,15,(19)(20)(21)25).…”

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confidence: 99%

Hantaviruses Direct Endothelial Cell Permeability by Sensitizing Cells to the Vascular Permeability Factor VEGF, while Angiopoietin 1 and Sphingosine 1-Phosphate Inhibit Hantavirus-Directed Permeability

Gavrilovskaya

Gorbunova

Mackow³

et al. 2008

J Virol

148

319

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Hantaviruses infect human endothelial cells and cause two vascular permeability-based diseases: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Hantavirus infection alone does not permeabilize endothelial cell monolayers. However, pathogenic hantaviruses inhibit the function of ␣v␤3 integrins on endothelial cells, and hemorrhagic disease and vascular permeability deficits are consequences of dysfunctional ␤3 integrins that normally regulate permeabilizing vascular endothelial growth factor (VEGF) responses. Here we show that pathogenic Hantaan, Andes, and New York-1 hantaviruses dramatically enhance the permeability of endothelial cells in response to VEGF, while the nonpathogenic hantaviruses Prospect Hill and Tula have no effect on endothelial cell permeability. Pathogenic hantaviruses directed endothelial cell permeability 2 to 3 days postinfection, coincident with pathogenic hantavirus inhibition of ␣v␤3 integrin functions, and hantavirus-directed permeability was inhibited by antibodies to VEGF receptor 2 (VEGFR2). These studies demonstrate that pathogenic hantaviruses, similar to ␣v␤3 integrin-deficient cells, specifically enhance VEGF-directed permeabilizing responses. Using the hantavirus permeability assay we further demonstrate that the endothelial-cell-specific growth factor angiopoietin 1 (Ang-1) and the platelet-derived lipid mediator sphingosine 1-phosphate (S1P) inhibit hantavirus directed endothelial cell permeability at physiologic concentrations. These results demonstrate the utility of a hantavirus permeability assay and rationalize the testing of Ang-1, S1P, and antibodies to VEGFR2 as potential hantavirus therapeutics. The central importance of ␤3 integrins and VEGF responses in vascular leak and hemorrhagic disease further suggest that altering ␤3 or VEGF responses may be a common feature of additional viral hemorrhagic diseases. As a result, our findings provide a potential mechanism for vascular leakage after infection by pathogenic hantaviruses and the means to inhibit hantavirus-directed endothelial cell permeability that may be applicable to additional vascular leak syndromes.

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“…In a series of clinical observations and in vitro experiments, Hayasaka et al and Terajima and Ennis suggested that increased capillary permeability observed in both H(C)PS and HFRS may be caused by a common immunopathological mechanism, i.e. hantavirus-specific cytotoxic CD8 + T lymphocytes, attacking endothelial cells presenting viral antigens on their surface [14,15].…”

mentioning

confidence: 99%

A unifying hypothesis and a single name for a complex globally emerging infection: hantavirus disease

Clément

Maes

Lagrou

et al. 2011

Eur J Clin Microbiol Infect Dis

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Increased permeability of human endothelial cell line EA.hy926 induced by hantavirus-specific cytotoxic T lymphocytes

Cited by 56 publications

References 49 publications

T Cells Are Not Required for Pathogenesis in the Syrian Hamster Model of Hantavirus Pulmonary Syndrome

T Cells Are Not Required for Pathogenesis in the Syrian Hamster Model of Hantavirus Pulmonary Syndrome

Hantaviruses Direct Endothelial Cell Permeability by Sensitizing Cells to the Vascular Permeability Factor VEGF, while Angiopoietin 1 and Sphingosine 1-Phosphate Inhibit Hantavirus-Directed Permeability

A unifying hypothesis and a single name for a complex globally emerging infection: hantavirus disease

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