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Chapter 3 : The Making of a Picornavirus Genome

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Abstract:

Picornavirus genomes have a unique structure, and they developed mechanisms of gene expression different from those of their prokaryotic counterparts. Genetic analyses have played a crucial role in deciphering the genome function of picornaviruses. One of the hallmarks in RNA virus research was the discovery of genetic recombination, an accomplishment received with great skepticism for several years. Cell-free synthesis, which duplicates essential steps of viral proliferation in the living cell, opened new strategies for studying individual steps of picornavirus replication in the absence of cell membrane barriers. In poliovirus (PV), the cloverleaf (CL) is followed by a short spacer of 24 nt that does not appear to engage in any base-pairing with adjacent nucleotides, as deduced from a detailed study with coxsackievirus B3 (CVB3). In cardioviruses and aphthoviruses, the genome segment preceding the internal ribosome entry site (IRES) differs completely from that of the enteroviruses. There is no CL; instead, a succession of elaborate RNA structures is followed by a long stretch of poly(C) that in encephalomyocarditis virus (EMCV) can exceed 600 nt (and plays a role in mouse pathogenesis). The most interesting trait of the poly proteins is that they contain the information for -cleavages, either as self-processing oligopeptide sequences (in aphtho- and cardioviruses) and/or as proteinases that are able to clip the polypeptide chain at their own N termini. Genetic complementation has been firmly established in picornavirus replication.

Citation: Wimmer E, Paul A. 2010. The Making of a Picornavirus Genome, p 33-55. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch3
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Figures

Image of Figure 1a.
Figure 1a.

(A) Genome structure of PV and processing of the polyprotein. The genome contains a long 5′ NTR that is covalently linked to VPg (a small open circle), a single ORF, and a short 3′ NTR with a poly(A) tail. The 5′ NTR contains four functional domains: the CL, spacer I, IRES, and spacer II. The polyprotein consists of one structural and two nonstructural domains. The processing of the polyprotein into precursor and mature proteins is illustrated. (B) Genome structure of a dicistronic PV. This dicistronic virus contains the PV IRES in the 5′ NTR and the EMCV IRES between domains P1 and P2 of the polyprotein. (C) Genome structure of a dicistronic PV containing a foreign protein. This dicistronic virus contains the PV IRES in the 5′ NTR followed by the coding sequence of a foreign gene (X), then the EMCV IRES, and finally the PV ORF, 3′ NTR, and poly(A) tail.

Citation: Wimmer E, Paul A. 2010. The Making of a Picornavirus Genome, p 33-55. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch3
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Image of Figure 1b.
Figure 1b.

(A) Genome structure of PV and processing of the polyprotein. The genome contains a long 5′ NTR that is covalently linked to VPg (a small open circle), a single ORF, and a short 3′ NTR with a poly(A) tail. The 5′ NTR contains four functional domains: the CL, spacer I, IRES, and spacer II. The polyprotein consists of one structural and two nonstructural domains. The processing of the polyprotein into precursor and mature proteins is illustrated. (B) Genome structure of a dicistronic PV. This dicistronic virus contains the PV IRES in the 5′ NTR and the EMCV IRES between domains P1 and P2 of the polyprotein. (C) Genome structure of a dicistronic PV containing a foreign protein. This dicistronic virus contains the PV IRES in the 5′ NTR followed by the coding sequence of a foreign gene (X), then the EMCV IRES, and finally the PV ORF, 3′ NTR, and poly(A) tail.

Citation: Wimmer E, Paul A. 2010. The Making of a Picornavirus Genome, p 33-55. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch3
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Image of Figure 2.
Figure 2.

Comparison of amino acid (aa) sequences of some picornaviral VPgs. The fully conserved amino acids are shown by a vertical box. The essential amino acids of PV are indicated with boxes (see text).

Citation: Wimmer E, Paul A. 2010. The Making of a Picornavirus Genome, p 33-55. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch3
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Image of Figure 3.
Figure 3.

The Yn-Xm-AUG motif and spacer II. The Yn-Xm-AUG motif is located partly in stem-loop VI of the PV IRES, as illustrated. Spacer II is between stem-loop VI and the initiating AUG of the polyprotein. The approximate location of the HRV initiation codon is also shown. Conserved sequences are boxed. , cryptic; , active; , codon within the ORF.

Citation: Wimmer E, Paul A. 2010. The Making of a Picornavirus Genome, p 33-55. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch3
Permissions and Reprints Request Permissions
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References

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