Amino acids substitutions in sigma 1 and mu 1 outer capsid proteins of a Vero cell-adapted mammalian orthoreovirus are required for optimal virus binding and disassembly

摘要

In a recent study, the serotype 3 Dearing strain of mammalian orthoreovirus was adapted to Vero cells; cells that exhibit a limited ability to support the early steps of reovirus uncoating and are unable to produce interferon as an antiviral response upon infection. The Vero cell-adapted virus (VeroAV) exhibits amino acids substitutions in both the sigma 1 and mu 1 outer capsid proteins but no changes in the sigma 3 protein. Accordingly, the virus was shown not to behave as a classical uncoating mutant. In the present study, an increased ability of the virus to bind at the Vero cell surface was observed and is likely associated with an increased ability to bind onto cell-surface sialic acid residues. In addition, the kinetics of mu 1 disassembly from the virions appears to be altered. The plasmid-based reverse genetics approach confirmed the importance of sigma 1 amino acids substitutions in VeroAV's ability to efficiently infect Vero cells, although mu 1 co-adaptation appears necessary to optimize viral infection. This approach of combining in vitro selection of reoviruses with reverse genetics to identify pertinent amino acids substitutions appears promising in the context of eventual reovirus modification to increase its potential as an oncolytic virus. (C) 2014 Elsevier B.V. All rights reserved.