Cleavage of the respiratory syncytial virus fusion protein is required for its surface expression: role of furin.
The fusion (F) glycoprotein of respiratory syncytial virus (RSV) is synthesized as a nonfusogenic precursor protein (F(0)), which during its migration to the cell surface is activated by cleavage into the disulfide-linked F(1) and F(2) subunits. In the present study, soluble secreted human furin produced by a recombinant baculovirus cleaved RSV F(0) into proteins the size of F(1) and F(2). Furthermore, cleavage of F(0) was partially inhibited in the furin defective LoVo cell line, in calcium depleted HEp-2 cells, and in HEp-2 cells treated with the furin inhibitor decanoyl-R-V-K-R-chloromethylketon. These findings strongly suggest an important role for furin in activation of the RSV F protein. The F(0) protein could not be detected on the surface of cells, in which F protein activation was inhibited, and RSV particles did not appear to be released from these cells. It thus seems that in contrast to the F proteins of most other paramyxoviruses, the RSV F(0) protein is very inefficient in reaching the cell surface or is unable to reach the cell surface and therefore cannot be incorporated into virus particles.
Department of Medical Microbiology and Immunology, Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 N, Copenhagen, Denmark. gb@kvl.dk
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Bolt
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Pedersen
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Birkeslund
D016367:Baculoviridae / Q000235:genetics / Q000378:metabolism; D045683:Furin; D015707:HN Protein; D006801:Humans; D011233:Precipitin Tests; D018357:Respiratory Syncytial Virus Infections / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity / Q000502:physiology*; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000378:metabolism*
D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G; D013381:Subtilisins; D045683:Furin