The Role of alpha5beta1 Integrin on Infection of Hantaan Virus in Fibroblasts

Park, Ho Sun

Abstract

Pathophysiological mechanism of hemorrhagic fever with renal syndrome(HFRS) is not fully understood. Major clinical findings of HFRS patients are widespread hemorrhage, acute renal failure and shock. Basic lesion is vascular injury with microvascular hemorrhage and relatively little inflammation. According to autopsy findings, renal medulla has focal hemorrhage, tubular necrosis and interstitial mononuclear infiltrates. Hantavirus pulmonary syndrome(HPS) caused by Sin Nombre virus which is known as a member of Hantavirus genus, characterized by rapidly progressive pulmonary edema, hypotension and interstitial pulmonary infiltrate with lymphocytes. The predominant cell type in the renal and pulmonary interstitium is a fibroblast and it participates in the healing process at injury site by secreting a large amount of extracellular matrix proteins. Cultured human lung fibroblasts and Mongolian gerbil fibroblasts were known as the good host cells to the hantaan virus. It is possible that not only endothelial cell but also fibroblast is a target of Hantaan virus and the fibroblast might be involved in the pathogenesis and the healing process in HFRS. Integrins are an adhesion molecule, and act as the receptors for many extracellular matrix proteins. Recently, there are many reports that cell surface integrins influence on some viral infections or reversely viruses influence on the expression of integrins. The alpha5beta1, integrin is a major receptor for the fibronectin which is an important extracellular matrix protein secreted by fibroblasts. In this study, the role of alpha5beta1 integrin on the infection of Hantaan virus was examined by using an anti-alpha5beta1 integrin antibody in chicken embryo fibroblasts(CEF) and Mongolian gerbil fibroblasts(MGF). CEF and MGF were treated with anti-alpha5beta1, integrin antibody during 30 minutes before viral infection and the culture supernatants were harvested 5 days after virus infection. The treatment of anti-alpha5beta1 integrin antibody on CEF reduced the viral titers about 30% when compared with the non-antibody treatment control CEF. In MGF, these viral titers were reduced by 36% and 68% according to the assay methods by FFU and ELISA, respectively. These results suggested that alpha5beta1 integrin might be act as a receptor for the Hantaan virus or blocking of alpha5beta1 integrin influence on the viral replication in CEF and MGF. To find out which suggestion is related with, further studies are going on.