Protease cleavage of reovirus capsid protein μ1/μ1C is blocked by alkyl sulfate detergents, yielding a new type of infectious subvirion particle

Kartik Chandran, Max L. Nibert

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Mammalian reovirus virions undergo partial disassembly of the outer capsid upon exposure to proteases in vitro, producing infectious subvirion particles (ISVPs) that lack protein σ3 and contain protein μ1/μ1C as endoprotease-generated fragments μ1δ/δ and Φ. ISVPs are thought to be required for two early steps in reovirus infection: membrane penetration and activation of the particle-bound vital transcriptase complexes. Genetic and biochemical evidence implicates outer-capsid protein μ1 in both these steps. To determine whether the cleavage of μ1/μ1C is relevant to the unique properties of ISVPs, we analyzed the properties of novel subvirion particles that lacked σ3 yet retained μ1/μ1C in an uncleaved but clearable form. These detergent-plus-protease subvirion particles (dpSVPs) were produced by treating virions with chymotrypsin in the presence of micellle-forming concentrations of alkyl sulfate detergents. Infections with dpSVPs in marine L or canine MDCK cells provided evidence that the cleavage of μ1/μ1C during viral entry into these cells is dispensable for reovirus infection. Additionally, dpSVPs behaved like ISVPs in their capacity to permeabilize lipid bilayers and to undergo transcriptase activation in vitro, supporting the conclusion that cleavage of μ1/μ1C to μ1δ/δ and Φ during viral entry is not required for either membrane penetration or transcriptase activation in cells. The capacity of alkyl sulfate detergents to inhibit the cleavage of μ1/μ1C in a reversible fashion suggests a specific association between virus particle and detergent micelles that may mimic virus particle- phospholipid membrane interactions during reovirus entry into cells.

Original languageEnglish (US)
Pages (from-to)467-475
Number of pages9
JournalJournal of virology
Volume72
Issue number1
StatePublished - Jan 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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