engleski

Immunereactions caused by Hantaan virus and Andes virus in MRC-5 and HEK 293 cells

Hantaviruses (HTV), genus Hantavirus, family Bunyaviridae are rodent-borne viruses that are associated with two main clinical diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Little is known about the immunopathogenesis in HTV infections, and especially why different HTV cause mainly kidney disorders, while others mostly affect the lungs. The aim of this study was to analyze some non-specific imunoreactions regulated by two viruses ; Hantaan virus (HFRS-causing) and Andes virus (HPS-causing) in two different cell types: human lung fibroblasts (MRC-5 cells) and human kidney cells (HEK293 cells). In lung fibroblasts we analyzed the gene expression for different cytokines/chemokines ; extracellular matrix and adhesion molecules (ECM) and NF-kB signal transductional pathway in the early phase of infection (six hours). In HEK293 cells we analyzed the genes involved in different apoptosis pathways and changes in ECM gene expression in two time points during infection (3 and 5 days). To compare expression profiles of genes in RNA samples we used Focused Gene Expression cDNA Array Analysis (GEArrays, SuperArray Bioscience, Frederick, MD, USA). Selected genes identified by GEArray analysis were also analyzed by RT-PCR to verify transcriptional responses. In MRC-5 cells Hantaan virus increased expression of interleukin (IL)-6 and IL-8, while Andes virus also influenced the gene expression of some growth factors. Both viruses increased gene expression for the members of Rel/NFkB/IkB family. In infected HEK293 cells we found increased gene expression of p53, BCL2-interacting killer and caspase 7. We also observed a decrease in gene expression for several metalloproteinases and their inhibitors, which are critical modulators of ECM. Our findings may direct future studies which should explain some mechanisms in immunopathogenesis of kidney and lung disorders during HFRS/HPS.

hantaviruses; immunology; cytokines; apoptosis; NF-kB; adhesion molecules

Rad je kao poster prezentiran i na skupu NIAID Research Conference, održanom od 24.-30.06.2006., Opatija, Hrvatska ; bez recenzije objavljen u Knizi sažetaka.