Conformational changes in the hepatitis A virus capsid in response to acidic conditions.
Low pH values encountered during uptake of viruses by receptor-mediated endocytosis have been shown to expose hydrophobic residues of many viruses and result in viral conformational changes leading to uncoating of the viral genome. An assay for hydrophobicity utilising the non-ionic detergent Triton X-114 was established, making use of metabolically-labelled hepatitis A virus (HAV). In this assay, hydrophilic proteins interact with the aqueous (buffer) phase, while hydrophobic proteins interact with the Triton (detergent) phase. HAV particles interact with the aqueous phase at neutral pH, whereas, under acidic conditions, HAV was found predominantly in the detergent phase. This indicates that the capsid of HAV undergoes conformational changes rendering the particle more hydrophobic under acidic conditions. A further two conformational changes were found in HAV on exposure to low pH, as detected by changes in buoyant density in CsCl gradients. These were maturation of provirions to virions and the formation of dense particles. These results may have implications for uncoating of the HAV RNA genome, and these conformational changes could represent intermediates in the viral uncoating process.
Bishop
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D000143:Acids / Q000494:pharmacology*; D002213:Capsid / Q000737:chemistry* / Q000187:drug effects; D004705:Endocytosis; D006507:Hepatovirus / Q000737:chemistry* / Q000187:drug effects / Q000254:growth & development; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D011487:Protein Conformation
D000143:Acids