Year: 2011
Type: article
Abstract: KONONCHIK JR, JOSEPH PETER.Assembly and Entry of Alphaviruses.(Under the direction of Dennis Brown.)Sindbis virus, the prototype virus for alphaviruses, is a membrane containing virus with T=4 icosahedral symmetry.It contains two icosahedral shells sandwiching a hostderived lipid bilayer.The outer shell consists of the glycoproteins E1 and E2 and the inner shell is made of capsid and along with the RNA make up the nucleocapsid.The symmetry of the particle has been shown to be directed by the nucleocapsid.Here, data is presented that supports this hypothesis.Using previously generated SV mutants containing furin protease sites at the base of the viral glycoproteins, E1 and E2, the last step of encapsulation can be inhibited.This is hypothesized to be a loss of capsid-glycoprotein interaction at the last critical step of encapsulation.As a result, the virus particles that normally release into the extracellular medium continue to recruit glycoproteins.This creates long tubular protrusions from the plasma membrane that release with agitation.Analysis of the tubular viruses shows assembly consistent with Casper and Klug's hypothesis that simple subunits (E1/E2 trimers in this case) can create icosahedral, tubular and planar symmetry.Recent crystal structures of soluble constructs of E1 and an E1-E2 fusion protein DEDICATION This work is dedicated to my wife Genevieve Anne Holzapfel.Together we have made it through some of the worst times and some of the best of times.I will never stop learning from her.
Author: Joseph P. Kononchik
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2523139477