Hepatitis A viius
serves as a model for picornaviruses m general These processes, described in general terms in Chapter 3, are summarized below and in Fig. 23-2.
The cell receptor for poliovirus is a novel member of the immunoglobulin superfamily, as are those for other picornaviruses (e.g., the adhesion protein TCAlVHhfor most rhinoviruses and some coxsackieviruses), in contrast to the integrin VLA-2 for certain echoviruses. Following adsorption, penetration, and intracellular uncoating, VPg is removed from the virion RNA by cellular enzymes. The virion RNA, acting as mRNA, is then translated without interruption into a single polyprotein, which is cleaved autocatalytically into the intermediates PI, P2, and P3. PI is then further cleaved to yield first VPO, VP I, and VP3 and finally the four structural proteins VP1, VP2, VP3, and VP4 (see Fig. 3-8). The P2 region codes for three nonstructural proteins including one with protease activity, and the P3 region codes for four proteins including the RNA-dependent RNA polymerase required for RNA replication.
Viral RNA synthesis takes place in a "replication complex" which comprises RNA templates and the virus-coded RNA polymerase and several other viral and cellular proteins, tightly associated with a newly assembled smooth cytoplasmic membrane structure. Synthesis of the complementary strand is initiated at the 3' terminus of the virion RNA and uses the protein VPg as a primer. The completed complementary strand in turn serves as a template for the synthesis of virion RNA, although the details of the process may differ. Most of the replicative intermediates found within the replication complex consist of a full-length complementary (minus sense) RNA molecule from which several nascent plus sense strands are being transcribed simul-
ypg — capsid proteins--nonstructural proteins
*—| VPO | VP3 I VP1 2A j2B| 2C |3A|%l 3C ] 3D [—
| Translation into polyprotein i Pt 1 P2 1
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