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In Vitro Disassembly of Influenza A Virus Capsids by Gradient Centrifugation
Published on: March 27, 2016
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Influenza A virus uses the aggresome processing machinery for host cell entry
Indranil Banerjee1, Yasuyuki Miyake2, Samuel Philip Nobs3
1Institute of Biochemistry, Eidgenossische Technische Hochschule (ETH) Zurich, Switzerland.
Science (New York, N.Y.)
|October 25, 2014
Summary
Influenza A virus (IAV) uncoating utilizes host cell aggresome machinery by mimicking misfolded proteins. This activates histone deacetylase 6 (HDAC6) and motor proteins, crucial for viral entry and infection.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Influenza A virus (IAV) entry requires uncoating of viral ribonucleoproteins (vRNPs) for nuclear replication.
- Following membrane fusion, vRNPs and matrix proteins dissociate in the cytosol.
Purpose of the Study:
- To investigate the mechanism of IAV capsid disassembly during cell entry.
- To determine if host cell machinery is involved in viral uncoating.
Main Methods:
- Investigated IAV capsid disassembly using biochemical assays and microscopy.
- Examined the role of host cell aggresome formation and associated proteins.
Main Results:
- IAV capsids mimic misfolded protein aggregates by displaying unanchored ubiquitin chains.
- This activates a histone deacetylase 6 (HDAC6)-dependent pathway, essential for uncoating.
- Microtubule- and actin-associated motor proteins (dynein, dynactin, myosin II) are required for efficient IAV entry.
Conclusions:
- IAV exploits the host cell's aggresome machinery for viral capsid disassembly.
- HDAC6 recruitment via ubiquitin-binding domains is critical for uncoating.
- Cytosolic motor proteins generate physical forces necessary for IAV cell entry.
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