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. 1997 Apr;71(4):3288–3292. doi: 10.1128/jvi.71.4.3288-3292.1997

Proteinase 3C-mediated processing of VP1-2A of two hepatitis A virus strains: in vivo evidence for cleavage at amino acid position 273/274 of VP1.

C Probst 1, M Jecht 1, V Gauss-Müller 1
PMCID: PMC191466  PMID: 9060697

Abstract

Two prominent features distinguish hepatitis A virus (HAV) from other members of the picornavirus family. A C-terminally prolonged precursor of the structural protein VP1 is incorporated into assembly intermediates (e.g., the provirion), and a single proteinase is contained within the HAV polyprotein. Using an in vivo expression system, we show that proteolytic liberation of VP1 from its precursors P1-2A and VP1-2A is catalyzed by the virus-encoded proteinase 3Cpro. Among the proposed cleavage sites within VP1-2A, the Glu/Ser pair found at VP1 amino acid position 273/274 of most HAV strains is efficiently processed, whereas proteolysis of the Val/Ser site of the attenuated HM175 strain is protracted. Two mutations within VP1-2A (Lys[297]Arg and Ser[330]Asn) had no effect on 3Cpro-mediated cleavage at this site. Additional sites in this region of VP1-2A can also be utilized as substrates by the proteinase, yet less efficiently, and might give rise to smaller and larger VP1 polypeptides also detected in HAV-infected cells.

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Selected References

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