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Published on: December 29, 2015
The alphavirus E3 glycoprotein functions in a clade-specific manner.
Anthony J Snyder1, Suchetana Mukhopadhyay
1Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana, USA.
Journal of Virology
|October 5, 2012
Summary
Alphavirus E3 glycoprotein is crucial for spike assembly and infectious particle formation. Chimeric viruses show that E3
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- Alphavirus particles possess surface glycoprotein spikes essential for host cell entry.
- Spike assembly involves interactions between five structural proteins: E3, E2, 6K, TF, and E1.
- The E3 glycoprotein acts as a signal sequence for protein translocation and is vital for virus maturation, but its role in spike formation is not fully understood.
Purpose of the Study:
- To investigate the specific roles of the E3 glycoprotein in alphavirus spike assembly and infectious particle formation.
- To elucidate the function of E3 beyond its signal sequence and maturation roles.
- To identify interactions between E3 and other viral proteins that regulate spike assembly.
Main Methods:
- Construction and analysis of chimeric alphaviruses with E3 glycoproteins exchanged between different species.
- Assessment of viral titers, particle morphology, and protein composition in chimeric viruses.
- Structure-function and revertant analyses to characterize E3 chimera function.
Main Results:
- Interchanging E3 between alphavirus species within the same clade resulted in viruses with similar titers and particle characteristics to parental viruses.
- Chimeric viruses with E3 from different clades exhibited reduced viral titers and abnormal particle morphology and composition.
- Identification of two critical interactions between E3 and the E2 glycoprotein regulating spike assembly.
Conclusions:
- The E3 glycoprotein plays a significant, previously underappreciated role in alphavirus spike assembly.
- E3's function in spike assembly is clade-specific, indicating evolutionary constraints.
- Specific E3-E2 interactions are essential for proper spike formation and infectious virion production.
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