UMA, M. and HEGDE, S. R. and RAO, P. P. and NAGALEKSHMI, K. and GAUTHAMI, S. and KUMAR, D. and HEGDE, N. R. (2018) A novel point mutation (L70P) inactivates poliovirus 3C protease. Acta virologica, 62 (01). pp. 68-77. ISSN 1336-2305

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Abstract

Poliovirus (PV) contains a single-stranded positive-sense RNA genome, which is translated into a single polyprotein. Viral proteases process this polyprotein to produce several individual as well as fused proteins. The major viral protease 3C cleaves at nine of the eleven cleavage sites. During the process of expressing PV 3ABC protein in Escherichia coli, we identified a 3C mutant (L70P), which lost its protease activity. This loss of function was confirmed by generating recombinant adenoviruses expressing mutant and wild-type 3C. Further, infectious PV could not be recovered from PV full-length cDNA containing the L70P mutation. However, 3C L70P mutant cDNA could complement a PV cDNA containing a 1AB deletion, producing a viable virus population containing defective complementing genomes. Structural analysis of the mutant protein indicated that the L70P mutation resulted in the loss of a hydrogen bond between two residues located within a loop between two β-sheets, potentially leading to strain on the catalytic site. We conclude that L70P inactivates 3C protease because of its close proximity to the 3C catalytic site.

Item Type:	Article
Subjects:	Animal Genetics and Genomics Infectious Diseases Inflammation Biology Reproductive Biology Genetic Engineering Bioinformatics
Depositing User:	Mr Harjit Singh
Date Deposited:	20 May 2019 08:33
Last Modified:	26 Jun 2019 11:09
URI:	http://niab.sciencecentral.in/id/eprint/60

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