The Effects of Hantaan Virus on Fibronectin and Matrix Metalloproteinase-3

ABSTRACT

The clinical symptoms and signs of hemorrhagic fever with renal syndrome (HFRS) are well known, but the pathophysiology caused by Hantaan virus is not fully understood yet. This study was designed to evaluate the effect of Hantaan virus on the regulation of extracellular matrix proteins. The changes of fibronectin, fibronectin receptor (alpha5beta1 integrin), the matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in Vero E6 cell line were observed. Hantaan virus induced the mRNA expression of fibronectin at day 7 after the infection but the surface expression of fibronectin receptor (alpha5beta1 integrin) was reduced. The mRNA expression of MMP-3 was increased at day 5 by 8-fold in the virus infected cells compared with the control cells, and continued to increase until day 9. However, the mRNA expression of TIMP-1 did not show any significant changes. The concentration of plasma fibronectin in the HFRS patients was measured by ELISA. The fibronectin levels were variable and could be divided into three groups low (14.8%), normal (62.9%) and high (22.2%) groups in comparison with normal range value. These results suggest that Hantaan virus should affect not only the infected cell itself but also the extracelluar matrix, which might play an important role in the pathogenesis.