Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses

被引:164
作者
Geimonen, E
Neff, S
Raymond, T
Kocer, SS
Gavrilovskaya, IN
Mackow, ER [1 ]
机构
[1] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA
[3] SUNY Stony Brook, Mol Cell Biol Program, Stony Brook, NY 11794 USA
[4] Vet Adm Med Ctr, Northport, NY 11768 USA
关键词
D O I
10.1073/pnas.192298899
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hantavinuses cause two human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Hantavinuses infect human endothelial cells but cause little or no damage to the infected endothelium. We analyzed with Affymetrix DNA Arrays (Santa Clara, CA) the endothelial cell transcriptional responses directed by hantaviruses associated with HPS [New York-1 virus (NY-1V)], HFRS [Hantaan virus (HTNV)], or by a hantavirus not associated with human disease [Prospect Hill virus (PHV)]. Hantavirus infections induced 117 cellular genes and repressed 25 genes by >3-fold, 4 days postinfection (p.i). Although >80% of cells were infected by each virus 1 day p.i., PHV induced or repressed 67 genes at this early time compared with three genes altered by HTNV or NY-1V. The early high-level induction of 24 IFN-stimulated genes by PHV (4- to 229-fold) represents a fundamental difference in the temporal regulation of cellular responses by pathogenic and nonpathogenic hantaviruses. Because all hantaviruses induced >23 IFN-stimulated genes at late times p.i., pathogenic hantaviruses appearto suppress early cellular IFN responses that are activated by nonpathogenic hantaviruses. At late times p.i., 13 genes were commonly induced by HTNV and NY-1V that were not induced by PHV. In contrast to NY-1V, HTNV uniquely induced a variety of chemokines and cell adhesion molecules (i.e., IL-8, IL-6, GRO-beta, ICAM), as well as two complement cascade-associated factors that may contribute to immune components of HFRS disease. NY-1V failed to induce most cellular chemokines directed by HTNV (3/14) or genes primarily activated by NF-kappaB. However, NY-1V uniquely induced beta3 integrin-linked potassium channels, which could play a role in HPS-associated vascular permeability. These studies provide a basic understanding of hantavirus-directed cellular responses that are likely to differentiate pathogenic and nonpathogenic hantaviruses, contribute to HFRS and HPS pathogenesis, and provide insight into disease mechanisms and potential therapeutic interventions.
引用
收藏
页码:13837 / 13842
页数:6
相关论文
共 46 条
  • [1] Aplin AE, 1998, PHARMACOL REV, V50, P197
  • [2] Tumor necrosis factor receptor-associated factors (TRAFs)
    Bradley, JR
    Pober, JS
    [J]. ONCOGENE, 2001, 20 (44) : 6482 - 6491
  • [3] BROXMEYER HE, 1993, J IMMUNOL, V150, P3448
  • [4] A mechanism for modulation of cellular responses to VEGF: Activation of the integrins
    Byzova, TV
    Goldman, CK
    Pampori, N
    Thomas, KA
    Bett, A
    Shattil, SJ
    Plow, EF
    [J]. MOLECULAR CELL, 2000, 6 (04) : 851 - 860
  • [5] Activation of NF-κB via the IκB kinase complex is both essential and sufficient for proinflammatory gene expression in primary endothelial cells
    Denk, A
    Goebeler, M
    Schmid, S
    Berberich, I
    Ritz, O
    Lindemann, D
    Ludwig, S
    Wirth, T
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (30) : 28451 - 28458
  • [6] Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays
    Der, SD
    Zhou, AM
    Williams, BRG
    Silverman, RH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (26) : 15623 - 15628
  • [7] DVORAK HF, 1995, AM J PATHOL, V146, P1029
  • [8] García-Sastre A, 1998, J VIROL, V72, P8550
  • [9] New York 1 and Sin Nombre viruses are serotypically distinct viruses associated with hantavirus pulmonary syndrome
    Gavrilovskaya, I
    LaMonica, R
    Fay, ME
    Hjelle, B
    Schmaljohn, C
    Shaw, R
    Mackow, ER
    [J]. JOURNAL OF CLINICAL MICROBIOLOGY, 1999, 37 (01) : 122 - 126
  • [10] GAVRILOVSKAYA I N, 1987, Mikrobiologicheskii Zhurnal (Kiev), V49, P71