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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Intracellular cleavage of human influenza a virus hemagglutinin and its inhibition.

Replication of human influenza A viruses and proteolytic cleavage of the viral glycoprotein HA0 --> HA1/2 were studied in passaged cultures of epithelial cells of the mucosal membrane of human large intestine (CACO-2 line), dog kidney cells (MDCK), and monkey kidney cells (CV-1). Cleavage of the viral glycoprotein HA0, synthesis of activated virions, multicycle virus infection, and effective production of viral foci under an agarose overlayer were found in CACO-2 cells. By pulse-chase labeling of viral glycoproteins, testing the sensitivity to endoglycosidase-H of the viral glycoproteins HA0 and HA1/2 synthesized, and inhibiting the HA0 proteolysis with brefeldin A, the HA0 --> HA1/2 proteolysis was established to occur in the late stages of intracellular transport in the trans-Golgi and plasma membrane areas of the cells. Proteolysis of the viral glycoprotein HA0 in CACO-2 cells was suppressed by aprotinin, a natural inhibitor of serine proteinases. Unlike MDCK and CV-1 cells resistant to apoptosis induced by influenza virus, CACO-2 cells retained their viability for 2-3 days after infection with human influenza A virus.[1]


  1. Intracellular cleavage of human influenza a virus hemagglutinin and its inhibition. Zhirnov, O.P., Vorobjeva, I.V., Ovcharenko, A.V., Klenk, H.D. Biochemistry Mosc. (2003) [Pubmed]
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