Journal of Biological Chemistry
Volume 274, Issue 8, 19 February 1999, Pages 4527-4531
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NUCLEIC ACIDS, PROTEIN SYNTHESIS, AND MOLECULAR GENETICS
Intrinsic Signals for the Assembly of Hepatitis A Virus Particles: ROLE OF STRUCTURAL PROTEINS VP4 AND 2A*

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Capsid assembly is the final event of virus replication, and its understanding is pivotal for the design of empty capsid-based recombinant vaccines and drug delivery systems. Although the capsid structure of several members of the picornavirus family has been elucidated, little is known about the structural elements governing the assembly process that is tightly associated with proteolytic processing of the viral polyprotein. Among the picornaviruses, hepatitis A virus (HAV) is unique in that it contains VP1-2A as a structural component and the small structural protein VP4, which argues for an assembly pathway different from that proposed for other picornaviruses. Using a recombinant system we show here that proteolytic processing of the HAV capsid proteins' precursor P1-2A is independent of the terminal domains 2A and VP4 of the substrate. However, both terminal domains play distinct roles in the assembly of viral particles. 2A as part of P1-2A is a primary signal for the assembly of pentameric structures which only further aggregate to empty viral capsids when VP4 is present as the N terminus of the precursor. Particle formation in the hepatovirus genus is thus regulated by two intrinsic signals that are distinct from those described for other picornaviruses.

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*

The work was supported by Deutsche Forschungsgemeinschaft (DFG) SFB 367, Project B7.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a fellowship granted by the Studienstiftung des Deutschen Volkes.

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Supported by a grant of the state of Schleswig-Holstein.