engleski

Early activation mechanisms in lung fibroblasts infected with hantaviruses

Lung disorders dominate in HPS, but are also found in HFRS, two diseases caused by viruses of the genus Hantavirus, family Bunyaviridae. Fibroblasts, in addition to their connective function, are important participants in the orchestration of acute and chronic inflammation, but to date, there is no evidence about their role in hantaviral infections. The aim of this study was to investigate the influences of two hantaviruses ; Hantaan virus (HFRS-causing) and Andes virus (HPS-causing) on lung fibroblasts. We analyzed the roles of some cytokines, and adhesion and extracellular matrix molecules in the early phase of infection. Additionally, we wanted to characterize the expression profiles of the genes involved in the NF-kB signal transductional pathway. Methods: We used Focused Gene Expression cDNA Array Analysis (GEArrays, SuperArray Bioscience, Frederick, MD, USA) to compare expression profiles of genes in RNA samples isolated from MRC-5 cells (human lung fibroblasts) 6 hours after the infection with Hantaan virus or Andes virus. Selected genes were also tested with RT-PCR. Results: Hantaan virus increased the gene expression for interleukin (IL)-6 and IL-8, while both viruses decreased the gene expression of bone morphogenetic protein 2 (BMP-2). We also found changes in the expression of many growth factors ; hepatocyte growth factor (HGF), colony-stimulating factor 1 (CSF-1) and fibroblast growth factor 11 (FGF-11). Both viruses influenced the gene expression for the members of Rel/NFkB/IkB family (nuclear factor related to kappa B binding protein-NFRKB) ; NFkB responsive genes (E-selectin) and adaptor proteins (TNF receptor-associated factor-TRAF-1). Andes virus downregulated the expression of the genes for integrin alpha 2, integrin alpha 3 and alpha 6, while changes were not found in infection with Hantaan virus. We also found that infection with both viruses had a substantial influence on the gene expression for matrix metalloproteinases and their tissue inhibitors. Conclusions: Our data show that lung fibroblasts have an active role in imunoreactions during hantaviral infections. Additional in vitro and clinical data are necessary to determine how the proposed changes in imunoreactions may influence pulmonary disorders caused by HFRS- and especially HPS-causing hantaviruses.

hantaviruses; lung fibroblasts; microarray

Pozvano predavanje na Medicinskom fakultetu u Renu, Nevada, SAD ; 22.07.