Structural and functional integrity of the coxsackievirus B3 oriR: spacing between coaxial RNA helices

Ooij, Mark J. M. van; Glaudemans, Dirk H. R. F.; Heus, Hans A.; Kuppeveld, Frank J. M. van; Melchers, Willem J. G.

doi:10.1099/vir.0.81558-0

Cited by 16 publications

(11 citation statements)

References 18 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, subsequent studies have shown that this domain is interchangeable between PV, CVB4 and HRV14 (129). In addition, it was shown that the 3’NTRs of poliovirus, HRV14 and CVB3 are not required for infectivity (23, 156, 163). In contrast those of FMDV and EMCV are essential for viral viability (40, 132).…”

Section: Factors Involved In the Initiation Of Protein-primed Rna mentioning

confidence: 99%

Initiation of protein-primed picornavirus RNA synthesis

Paul

Wimmer

2015

Virus Research

View full text Add to dashboard Cite

Plus strand RNA viruses use different mechanisms to initiate the synthesis of their RNA chains. The Picornaviridae family constitutes a large group of plus strand RNA viruses that possess a small terminal protein (VPg) covalently linked to the 5’-end of their genomes. The RNA polymerases of these viruses use VPg as primer for both minus and plus strand RNA synthesis. In the first step of the initiation reaction the RNA polymerase links a UMP to the hydroxyl group of a tyrosine in VPg using as template a cis-replicating element (cre) positioned in different regions of the viral genome. In this review we will summarize what is known about the intiation reaction of protein-primed RNA synthesis by the RNA polymerases of the Picornaviridae. As an example we will use the RNA polymerase of poliovirus, the prototype of Picornaviridae. We will also discuss models of how these nucleotidylylated protein primers might be used, together with viral and cellular replication proteins and other cis-replicating RNA elements, during minus and plus strand RNA synthesis.

show abstract

Section: Factors Involved In the Initiation Of Protein-primed Rna mentioning

confidence: 99%

Initiation of protein-primed picornavirus RNA synthesis

Paul

Wimmer

2015

Virus Research

View full text Add to dashboard Cite

show abstract

“…The viral RNA‐dependent RNA polymerase 3D needs to bind the terminus of the 3′UTR to initiate minus strand RNA synthesis. Thus, the 3′UTR plays an important role in viral replication and pathogenesis (Melchers et al ., 1997; Mirmomeni et al ., 1997; van Ooij et al ., 2006). The CVB3 3′UTR contains three stem‐loops named X, Y and Z, where X and Y interact to form a ‘kissing pair’ tertiary structure (Fig.…”

Section: Introductionmentioning

confidence: 99%

Specific interaction of HeLa cell proteins with coxsackievirus B3 3'UTR: La autoantigen binds the 3' and 5'UTR independently of the poly(A) tail

et al. 2007

View full text Add to dashboard Cite

SummaryCoxsackievirus B3 (CVB3) is a positive, singlestranded RNA virus. The secondary structure of the 3Ј untranslated region (3ЈUTR) of CVB3 RNA consists of three stem-loops and is followed by a poly(A) tail sequence. These stem-loop structures have been suggested to participate in the regulation of viral replication through interaction with cellular proteins that are yet to be identified. In this study, by competitive UV cross-linking using mutated 3ЈUTR probes we have demonstrated that the poly(A) tail is essential for promoting HeLa cell protein interactions with the 3ЈUTR because deletion of this sequence abolished most of the protein interactions. Unexpectedly, mutations that disrupted the tertiary loop-loop interactions without affecting the stem-loops did not apparently affect these protein interactions, indicating that secondary structure rather than the highorder structure may play a major role in recruiting these RNA binding proteins. Among the observed 3ЈUTR RNA binding proteins, we have confirmed a 52 kDa protein as the human La autoantigen by using purified recombinant protein and a polyclonal La antibody. This protein can interact with both the 3Ј and 5ЈUTRs independently of the poly(A) tail. Further analysis by two-stage UV cross-linking, we found that the 3Ј and 5ЈUTR sequences may share the same binding site on the La protein.

show abstract

“…It was possible that the low tolerance to mutation of CVB3 was caused by the presence of a lowerfidelity RNA-dependent RNA polymerase (RdRp) in terms of ribavirin incorporation, since at any given concentration of ribavirin, more mutagenesis would occur. To investigate this possibility, we purified the RdRps from both PV and CVB3 (12,32) and each was incubated with a previously described substrate (sym/ sub) and either the "correct" nucleotide or ribavirin triphosphate (RTP) (3,15). Examination of ribavirin incorporation revealed that CVB3 RdRp incorporated ribavirin much less efficiently than PV RdRp (Fig.…”

mentioning

confidence: 99%

Mutational Robustness of an RNA Virus Influences Sensitivity to Lethal Mutagenesis

Graci

Gnädig

Galarraga

et al. 2012

J Virol

View full text Add to dashboard Cite

The ability to extinguish a viral population of fixed reproductive capacity by causing small changes in the mutation rate is referred to as lethal mutagenesis and is a corollary of population genetics theory. Here we show that coxsackievirus B3 (CVB3) exhibits reduced mutational robustness relative to poliovirus, manifesting in enhanced sensitivity of CVB3 to lethal mutagens that is dependent on the size of the viral population. We suggest that mutational robustness may be a useful measure of the sensitivity of a virus to lethal mutagenesis. RNA virus genomes are replicated at mutation rates orders of magnitude higher than DNA genomes (10, 27) and exist as heterogeneous populations of genetically distinct yet related genomes. Attempts to define these populations have relied upon population genetics theory (5,6,34,35); unfortunately, little empirical evidence exists validating these theories in vivo (30).Population genetics theory predicts a log-linear relationship between the genomic mutation rate and the fecundity (average number of progeny generated per infectious cycle) needed to avoid extinction and defines a theoretical "extinction threshold" (6). A corollary of this theory is lethal mutagenesis, the ability to drive a viral population to extinction by increasing the error frequency (13).A high mutation rate can negatively affect viral fitness and may drive a population to extinction. However, the deleterious effects of a high mutation rate may differ between viruses depending on their mutational robustness, i.e., the constancy of a phenotype in the face of deleterious mutations (26). A more robust population is able to minimize the deleterious effects of a high mutation rate by opting not to maximize fitness, a phenomenon termed "survival of the flattest" (35). Previous studies have suggested that the distributions of mutational effects between DNA and RNA virus genomes are similar (25). Therefore, the mutational robustness of a virus might be expected to be similar to that of closely related viruses.We investigated the mutational robustness of two closely related enteroviruses, poliovirus (PV) and coxsackievirus B3 (CVB3), which employ similar replication strategies and genome organizations and exhibit 59% polyprotein identity (74% similarity) as shown by BLAST analysis (GenBank accession numbers Q5UEA2 and P03300). To compare the characteristics of mutational robustness of these two viruses, we examined the response of PV (Mahoney) and of CVB3 (CVB3/0) to increasing concentrations of the mutagenic nucleoside ribavirin (Fig. 1A). Infection was performed under conditions that included a low multiplicity of infection (MOI) so that the cumulative effect of increased mutation frequency could be observed over two or more replicative cycles. CVB3 was observed to be considerably more sensitive than PV to ribavirin treatment at 0.5 mM or greater. Dramatically increased sensitivity was not observed under conditions of high MOI (Fig. 1B), consistent with the deleterious effect of mutation being reversed by populati...

show abstract

Structural and functional integrity of the coxsackievirus B3 oriR: spacing between coaxial RNA helices

Cited by 16 publications

References 18 publications

Initiation of protein-primed picornavirus RNA synthesis

Initiation of protein-primed picornavirus RNA synthesis

Specific interaction of HeLa cell proteins with coxsackievirus B3 3'UTR: La autoantigen binds the 3' and 5'UTR independently of the poly(A) tail

Mutational Robustness of an RNA Virus Influences Sensitivity to Lethal Mutagenesis

Contact Info

Product

Resources

About