Picornavirus Morphogenesis

Jiang, Ping; Liu, Ying; Ma, Hongyang; Paul, Aniko V.; Wimmer, Eckard

doi:10.1128/mmbr.00012-14

Cited by 199 publications

(209 citation statements)

References 213 publications

(265 reference statements)

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“…3B, synplot2 predicts the location of the cis-acting elements Cre, RNase L ci, and α and β in genomes of 200 members of the C-Enterovirus genus (32). However, these structural elements do not play a role in PV encapsidation (12,35), and no other regions have significantly reduced (P < 0.001) synonymous site variation. We guess that synonymous changes have likely been saturated since the PV ancestral strain diverged from Coxsackie viruses (12).…”

Section: Resultsmentioning

confidence: 99%

“…4II: perhaps by condensation of capsid precursors ("pentamers") around the genome (49), followed by virion maturation (8). Previous studies have elucidated PV CP assembly in great detail (35), but the role of the PV genome in these steps remains uncertain (Discussion). We have borrowed the term cocondensation from other publications (50,51), as it indicates the progression of delicate steps between CP and the cognate genome (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…3). The 5'-and 3'-terminal RNA segments do not determine assembly specificity, as was shown (35,52). Domain P1 has also been omitted because it does not play any role in morphogenesis based on properties of PV "defective interfering particles" (DI particles) (53,54).…”

Section: Resultsmentioning

confidence: 99%

“…3F, we added Table S3, which depicts the amount of synonymous changes from PV1(M) as a percentage of total nucleotides in the coding domain P1, P2, and P3 (36). Whereas the number of natural synonymous changes in the PVs and CAV20 is large, the changes acquired in P(1+2+3) Max In PV-infected cells, icosahedral "procapsids" (also known as "empty capsids") (35,44) are formed that, remarkably, are void of viral or cellular RNAs. These procapsids are structurally closely related to PV virions (8), but the precise role of procapsids in PV morphogenesis is still unknown (Discussion).…”

Section: Resultsmentioning

confidence: 99%

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Limits of variation, specific infectivity, and genome packaging of massively recoded poliovirus genomes

Song¹,

Gorbatsevych²,

Liu³

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Computer design and chemical synthesis generated viable variants of poliovirus type 1 (PV1), whose ORF (6,189 nucleotides) carried up to 1,297 "Max" mutations (excess of overrepresented synonymous codon pairs) or up to 2,104 "SD" mutations (randomly scrambled synonymous codons). "Min" variants (excess of underrepresented synonymous codon pairs) are nonviable except for P2 Min , a variant temperature-sensitive at 33 and 39.5 • C. Compared with WT PV1, P2 Min displayed a vastly reduced specific infectivity (si) (WT, 1 PFU/118 particles vs. P2 Min , 1 PFU/35,000 particles), a phenotype that will be discussed broadly. Si of haploid PV presents cellular infectivity of a single genotype. We performed a comprehensive analysis of sequence and structures of the PV genome to determine if evolutionary conserved cis-acting packaging signal(s) were preserved after recoding. We showed that conserved synonymous sites and/or local secondary structures that might play a role in determining packaging specificity do not survive codon pair recoding. This makes it unlikely that numerous "cryptic, poliovirus | genome recoding | packaging signal | specific infectivity T he capsid precursor P1 (881 amino acids) of type 1 poliovirus (PV), mapping to the N terminus of the polyprotein (PP) (Fig. 1A), can be encoded in 10 442 ways (1) due to the degenerate genetic code. The tiniest fraction of these possible sequences defines PV, the cause of poliomyelitis. PV occurs in three serotypes, of which the most neurovirulent type 1 Mahoney [PV1(M)], the main viral species analyzed in this study, was isolated in 1941 from pooled feces of three healthy children (2).Genome sequence (3, 4) and gene organization (3) of PV1(M) revealed highly complex structures in its 5'-terminal nontranslated region (5'-NTR), followed by a single ORF encoding the PP, followed by a complex 3'-heteropolymeric region and poly(A) tail (Fig. 1A) (5, 6). The PP (7) is an active molecule that cleaves itself into ∼29 polypeptides by two viral proteinases (2A pro and 3C pro /3CD pro ) and an enzyme-independent maturation cleavage (Fig. 1A) (5,6,8).Capsid domain P1 controls the identity of PV by determining virion structure (9), serotype identity (10), and interaction with the cellular receptor CD155 (10). Since PV replicates as quasispecies at an error rate of ∼10 −4 (11), the following questions arise: How conserved is its synonymous sequence given the astronomical number of alternative possibilities? What encoding could have coevolved that would be optimal to specify 881 capsid residues?If PV, a member of the genus Enterovirus of Picornaviridae, is an evolutionary descendant of C-cluster Coxsackie viruses (C-CAVs) (12), the evolution of PV nucleotide sequences was constrained as it adhered to the basic architecture of C-CAVs, its evolutionary parents (13). A second well-known restriction of sequence variability in ORFs is "codon bias" (14), the unequal use of synonymous codons. Encoding the PV1 P1 domain with an excess of "rarely used" (human) synonymous codons results in a ...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Limits of variation, specific infectivity, and genome packaging of massively recoded poliovirus genomes

Song¹,

Gorbatsevych²,

Liu³

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…VP1 subunits are clustered around fivefold axes, and VP2 and VP3 form hetero-hexamers around icosahedral threefold axes. Unlike in the related picornaviruses and dicistroviruses, capsid protein VP3 of SBPV contains a C-terminal extension that folds into a globular protruding (P) domain positioned at the virion surface (10)(11)(12)(13). At neutral pH, the P domains form "crowns" on the virion surface around each fivefold axis of the virus.…”

mentioning

confidence: 99%

Cryo-EM study of slow bee paralysis virus at low pH reveals iflavirus genome release mechanism

Kalynych

Füzik

Přidal

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Viruses from the family Iflaviridae are insect pathogens. Many of them, including slow bee paralysis virus (SBPV), cause lethal diseases in honeybees and bumblebees, resulting in agricultural losses. Iflaviruses have nonenveloped icosahedral virions containing single-stranded RNA genomes. However, their genome release mechanism is unknown. Here, we show that low pH promotes SBPV genome release, indicating that the virus may use endosomes to enter host cells. We used cryo-EM to study a heterogeneous population of SBPV virions at pH 5.5. We determined the structures of SBPV particles before and after genome release to resolutions of 3.3 and 3.4 Å, respectively. The capsids of SBPV virions in low pH are not expanded. Thus, SBPV does not appear to form "altered" particles with pores in their capsids before genome release, as is the case in many related picornaviruses. The egress of the genome from SBPV virions is associated with a loss of interpentamer contacts mediated by N-terminal arms of VP2 capsid proteins, which result in the expansion of the capsid. Pores that are 7 Å in diameter form around icosahedral threefold symmetry axes. We speculate that they serve as channels for the genome release. Our findings provide an atomic-level characterization of the genome release mechanism of iflaviruses.electron microscopy | uncoating | honeybee | structure | virus

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Interacting motif networks located in hotspots associated with RNA release are conserved in Enterovirus capsids

2017

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Enteroviruses are responsible for a multitude of human diseases. Expansion of the virus capsid is associated with a cascade of conformational changes that allow the subsequent release of RNA. For the first time, this study presents a comprehensive bioinformatic screen for the prediction of interacting motifs within intraprotomer interfaces and across respective interfaces surrounding the fivefold and twofold axes. The results identify a network of conserved motif residues involved in interactions in enteroviruses that may be critical to capsid stabilisation, providing guidelines towards developing antivirals that interfere with viral expansion during RNA release.

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Picornavirus Morphogenesis

Cited by 199 publications

References 213 publications

Limits of variation, specific infectivity, and genome packaging of massively recoded poliovirus genomes

Limits of variation, specific infectivity, and genome packaging of massively recoded poliovirus genomes

Cryo-EM study of slow bee paralysis virus at low pH reveals iflavirus genome release mechanism

Interacting motif networks located in hotspots associated with RNA release are conserved in Enterovirus capsids

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