FWIW -
Antiviral Effect of N-Butyldeoxynojirimycin against Bovine Viral Diarrhea Virus Correlates with Misfolding of E2 Envelope Proteins and Impairment of Their Association into E1-E2 Heterodimers
Norica Branza-Nichita,1,2 David Durantel,1 Sandra Carrouée-Durantel,1 Raymond A. Dwek,1 and Nicole Zitzmann1,*
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom,1 and Institute of Biochemistry, Sector 6, Bucharest, Romania2
Received 28 November 2000/Accepted 29 January 2001
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BVDV has been suggested as a model for HCV since both viruses share molecular and virological features, such as similar genome organizations, replication strategies, and protein functions (24). In this study we show for the first time that BVDV and HCV have a common dependence on calnexin for the folding of their envelope glycoproteins. BVDV E1 and E2 associate rapidly with calnexin and dissociate at different rates. The disulfide-dependent folding of E2 is fast, while E1 folds rather slowly, as judged by the longer interaction with calnexin. The inhibition of calnexin binding to the envelope proteins by -glucosidase inhibitors leads to E2 (and probably E1) misfolding and a decrease in the formation of E1-E2 heterodimers.
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Treatment with -glucosidase inhibitors affect the life cycles of other enveloped viruses by inducing misfolding of viral structural proteins. For example, the V1-V2 loop of human immunodeficiency virus gp120, which is involved in virus binding to host cells, has an altered conformation in the presence of NB-DNJ, and this correlates with inhibition of virus entry into the target cells (11). Similarly, recent studies have shown that correct N-glycan trimming is necessary for the secretion of HBV virions and that proper folding and transport of the HBV M and L proteins depend upon the interaction with calnexin (3, 29, 30). The generality of these effects to other viruses remains to be established, for it crucially depends on their envelope glycoproteins using the calnexin-mediated folding pathway.
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Complete article ....
jvi.asm.org
(note:this topic is way over my head - so I could
be paddling the wrong way)
John McCarthy |
