Pneumococcal Carriage

Crook, Derrick W.; Brueggemann, Angela B.; Sleeman, Karen; Peto, Timothy E. A.

doi:10.1128/9781555816537.ch9

Cited by 23 publications

(22 citation statements)

References 56 publications

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“…The alignment construction was constrained by domain borders, most of which were delimited by known and predicted cleavage sites that are recognized by viral proteases in the polyprotein (46). Data sets.…”

Section: Methodsmentioning

confidence: 99%

“…We extensively tested DEmARC on the proteome of the Picornaviridae (29), one of the most diverse and well-studied RNA virus families (23,59) with numerous species that has been developed by one of the most active SGs (36,37,64). The picornavirus genome is a singlestranded positive-sense RNA (ssRNAϩ) with a single open reading frame that encodes a polyprotein (46,50) flanked by two untranslated regions, 5=-UTR and 3=-UTR (69). The consistency and stability of the obtained results were evaluated by analyzing various data set derivatives which were compiled by varying the amount and/or the diversity of the input data, the alignment construction method, the measure of pairwise similarity, or a combination of parameters.…”

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confidence: 99%

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Partitioning the Genetic Diversity of a Virus Family: Approach and Evaluation through a Case Study of Picornaviruses

Lauber

Gorbalenya

2012

J Virol

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The recent advent of genome sequences as the only source available to classify many newly discovered viruses challenges the development of virus taxonomy by expert virologists who traditionally rely on extensive virus characterization. In this proof-ofprinciple study, we address this issue by presenting a computational approach (DEmARC) to classify viruses of a family into groups at hierarchical levels using a sole criterion-intervirus genetic divergence. To quantify genetic divergence, we used pairwise evolutionary distances (PEDs) estimated by maximum likelihood inference on a multiple alignment of family-wide conserved proteins. PEDs were calculated for all virus pairs, and the resulting distribution was modeled via a mixture of probability density functions. The model enables the quantitative inference of regions of distance discontinuity in the family-wide PED distribution, which define the levels of hierarchy. For each level, a limit on genetic divergence, below which two viruses join the same group, was objectively selected among a set of candidates by minimizing violations of intragroup PEDs to the limit. In a case study, we applied the procedure to hundreds of genome sequences of picornaviruses and extensively evaluated it by modulating four key parameters. It was found that the genetics-based classification largely tolerates variations in virus sampling and multiple alignment construction but is affected by the choice of protein and the measure of genetic divergence. In an accompanying paper (C. Lauber and A. E. Gorbalenya, J. Virol. 86:3905-3915, 2012), we analyze the substantial insight gained with the genetics-based classification approach by comparing it with the expert-based picornavirus taxonomy.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Partitioning the Genetic Diversity of a Virus Family: Approach and Evaluation through a Case Study of Picornaviruses

Lauber

Gorbalenya

2012

J Virol

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“…All picornaviruses encode 3C pro , which carries out a primary cleavage between 2C and 3A and secondary processing of the [P1-2A], [2BC] and P3 precursors. In FMDV, 3C pro also cleaves between 2B and 2C (for review see Martĩnez-Salas & Ryan, 2010). Aside from the processing sites within the viral polyprotein itself, the enzyme also modifies host cell proteins (Belsham et al, 2000;Li et al, 2001).…”

Section: The Fmdv Genomementioning

confidence: 99%

“…Thus two major outcomes are possible; either translation terminates at this point, or, translation effectively 'reinitiates' to synthesize the downstream sequences. The latter case would entail; (a) egress of eRF1/3 from the A site, (b) ingress of prolyl-tRNA into the A site, (c) translocation of prolyltRNA to the P site and (d) entry of the next aminoacyl-tRNA (for in-depth reviews of the model see Ryan et al, 2002;Martĩnez-Salas & Ryan, 2010;.…”

Section: The Cleavage Mechanismmentioning

confidence: 99%

“…The 5' UTR, of approximately 1,300 nucleotides (nt) contains sequence elements controlling the replication of viral RNA, packaging of RNA into capsids, and translation of the viral polyprotein. Preceding the ORF is a type II internal ribosome entry site (IRES), crucial for the cap-independent initiation of translation (for reviews see Jackson et al, 1990;Martĩnez-Salas & Ryan, 2010). The 3' UTR is about 90 nt long and is thought to contain cis-acting elements Fig.…”

Section: The Fmdv Genomementioning

confidence: 99%

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Translating 2A Research into Practice

Luke¹

2012

Innovations in Biotechnology

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NMR analysis of the interaction of picornaviral proteinases Lb and 2A with their substrate eukaryotic initiation factor 4GII

et al. 2015

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Messenger RNA is recruited to the eukaryotic ribosome by a complex including the eukaryotic initiation factor (eIF) 4E (the cap‐binding protein), the scaffold protein eIF4G and the RNA helicase eIF4A. To shut‐off host–cell protein synthesis, eIF4G is cleaved during picornaviral infection by a virally encoded proteinase; the structural basis of this reaction and its stimulation by eIF4E is unclear. We have structurally and biochemically investigated the interaction of purified foot‐and‐mouth disease virus (FMDV) leader proteinase (Lbpro), human rhinovirus 2 (HRV2) 2A proteinase (2Apro) and coxsackievirus B4 (CVB4) 2Apro with purified eIF4GII, eIF4E and the eIF4GII/eIF4E complex. Using nuclear magnetic resonance (NMR), we completed 13C/15N sequential backbone assignment of human eIF4GII residues 551–745 and examined their binding to murine eIF4E. eIF4GII551–745 is intrinsically unstructured and remains so when bound to eIF4E. NMR and biophysical techniques for determining stoichiometry and binding constants revealed that the papain‐like Lbpro only forms a stable complex with eIF4GII551–745 in the presence of eIF4E, with K D values in the low nanomolar range; Lbpro contacts both eIF4GII and eIF4E. Furthermore, the unrelated chymotrypsin‐like 2Apro from HRV2 and CVB4 also build a stable complex with eIF4GII/eIF4E, but with K D values in the low micromolar range. The HRV2 enzyme also forms a stable complex with eIF4E; however, none of the proteinases tested complex stably with eIF4GII alone. Thus, these three picornaviral proteinases have independently evolved to establish distinct triangular heterotrimeric protein complexes that may actively target ribosomes involved in mRNA recruitment to ensure efficient host cell shut‐off.

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Pneumococcal Carriage

Cited by 23 publications

References 56 publications

Partitioning the Genetic Diversity of a Virus Family: Approach and Evaluation through a Case Study of Picornaviruses

Partitioning the Genetic Diversity of a Virus Family: Approach and Evaluation through a Case Study of Picornaviruses

Translating 2A Research into Practice

NMR analysis of the interaction of picornaviral proteinases Lb and 2A with their substrate eukaryotic initiation factor 4GII

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