Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-5-20
pubmed:abstractText
Experiments in cell-free systems have demonstrated that the VP5 cleavage fragment of the rotavirus spike protein, VP4, undergoes a foldback rearrangement that translocates three clustered hydrophobic loops from one end of the molecule to the other. This conformational change resembles the foldback rearrangements of enveloped virus fusion proteins. By recoating rotavirus subviral particles with recombinant VP4 and VP7, we tested the effects on cell entry of substituting hydrophilic for hydrophobic residues in the clustered VP5 loops. Several of these mutations decreased the infectivity of recoated particles without preventing either recoating or folding back. In particular, the V391D mutant had a diminished capacity to interact with liposomes when triggered to fold back by serial protease digestion in solution, and particles recoated with this mutant VP4 were 10,000-fold less infectious than particles recoated with wild-type VP4. Particles with V391D mutant VP4 attached normally to cells and internalized efficiently, but they failed in the permeabilization step that allows coentry of the toxin alpha-sarcin. These findings indicate that the hydrophobicity of the VP5 apex is required for membrane disruption during rotavirus cell entry.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1098-5514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6200-7
pubmed:dateRevised
2011-3-3
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Effect of mutations in VP5 hydrophobic loops on rotavirus cell entry.
pubmed:affiliation
Laboratory of Molecular Medicine, Children's Hospital, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural