title: The Low pH-Dependent Entry of Avian Reovirus Is Accompanied by Two Specific Cleavages of the Major Outer Capsid Protein &mu;2C
abstract: Avian reoviruses are capable of inducing rapid and extensive syncytium formation, a process that occurs preferentially under conditions of neutral or alkaline pH. In order to ascertain whether the membrane fusion-inducing capability of avian reovirus confers a pH-independent entry mechanism on the virus, virus entry was investigated using internalization assays and several lysomotropic agents that inhibit endosomal acidification. The ability of avian reovirus to infect cells was severely restricted under all conditions that prevented endosomal acidification. The decreased infection efficiency in the presence of the lysomotropic agents correlated with an inhibition in the proteolytic processing of the major outer capsid protein &mu;2C. The importance, with respect to virus infection, of the low pH-dependent cleavage of the avian reovirus &mu;2C protein was confirmed by demonstrating that infectious subviral particles, generated by proteolytic processing in vitro, were capable of efficiently infecting cells in the presence of the lysomotropic agents. These results indicated that avian reovirus entry-specific membrane interactions are largely dependent on an endosome-mediated proteolytic processing of the virus particle, suggesting that the syncytium-inducing property of the sigma3 protein is not sufficient to promote virus uptake. Furthermore, avian reovirus internalization was associated with two distinct cleavages of the major outer capsid protein &mu;2C, unlike the entry-specific processing of the analagous mammalian reovirus major outer capsid protein &mu;1C. The &mu;2C cleavages occured sequentially and appeared to involve distinct cleavage specificities. Moreover, the second cleavage event was observed to be both virus strain- and cell type-independent, suggesting that the cleavage is both specific and biologically significant.
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, B3H4H7, Canada
authors.initials: R
authors.lastname: Duncan