The glycoproteins of Marburg and Ebola virus and their potential roles in pathogenesis

Filoviruses cause systemic infections that can lead to severe hemorrhagic f ever in human and non-human primates. The primary target of the virus appea rs to be the mononuclear phagocytic system. As the virus spreads through th e organism, the spectrum of target cells increases to include endothelial c ells, fibroblasts, hepatocytes, and many other cells. There is evidence tha t the filovirus glycoprotein plays an important role in cell tropism, sprea d of infection, and pathogenicity. Biosynthesis of the glycoprotein forming the spikes on the virion surface involves cleavage by the host cell protea se furin into two disulfide linked subunits GP(1) and GP(2). GP(1) is also shed in soluble form from infected cells. Different strains of Ebola virus show variations in the cleavability of the glycoprotein, that may account f or differences in pathogenicity, as has been observed with influenza viruse s and paramyxoviruses. Expression of the spike glycoprotein of Ebola virus, but not of Marburg virus, requires transcriptional editing. Unedited GP mR NA yields the nonstructural glycoprotein sGP, which is secreted extensively from infected cells. Whether the soluble glycoproteins GP(1) and sGP inter fere with the humoral immune response and other defense mechanisms remains to be determined.