Genetic analysis of the attenuation phenotype of poliovirus type 1

Omata, Toshiko; Kohara, Michinori; Kuge, Shusuke; Komatsu, Toshihiko; Abe, S.; Semler, Bert L.; Kameda, Atsushi; Itoh, Hidenori; Arita, Mined; Wimmer, Eckard

doi:10.1128/jvi.58.2.348-358.1986

Cited by 180 publications

(147 citation statements)

References 39 publications

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“…As a positive control for RdRp, a poliovirus cDNA encoding polymerase was also constructed as follows: pVM(1)pDS306(T) 33 containing a full-length cDNA of poliovirus (Mahoney strain) was a generous gift from Dr. A. Nomoto (University of Tokyo). Baculovirus transfer vector pAcPol3A*BCD was constructed according to Neufeld et al 34 pVM(1)pDS306(T) was digested with AlwNI, filled in with a Klenow fragment, ligated with NcoI linker, digested with NcoI and a 2.4-kb fragment corresponding to 3A*, 3B, 3C, and 3D (* designates coding sequences for an incomplete protein), and purified.…”

Section: Methodsmentioning

confidence: 99%

Expression of Hepatitis C Virus Ns5b Protein: Characterization of Its Rna Polymerase Activity and Rna Binding

Ishii¹,

Tanaka²,

Yap³

et al. 1999

Hepatology

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The nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) is considered to possess RNA-dependent RNA polymerase (RdRp) activity and to play an essential role for the viral replication. In this study, we expressed the NS5B protein of 65 kd by a recombinant baculovirus. With the highly purified NS5B protein, we established an in vitro system for RdRp activity by using poly(A) as a template and a 15-mer oligo(U) (oligo(U) 15 ) as a primer. Optimal conditions of temperature and pH for primer-dependent polymerase activity of the NS5B were 32ЊC and pH 8. Hepatitis C virus (HCV) is the major etiologic agent of both posttransfusion and sporadic non-A, non-B hepatitis throughout the world. 1-3 HCV infection often leads to persistence, resulting in chronic hepatitis, and develops into hepatocellular carcinoma. Although the incidence of infection with HCV was drastically decreased by introduction of an efficient blood screening system, 1% to 2% of the worldwide population are already infected with HCV. Furthermore, seroepidemiological studies indicated that there is a clear correlation between infection with HCV and the development of hepatocellular carcinoma. It is therefore very important to develop anti-HCV agents with different antiviral mechanisms for the treatment of liver diseases associated with HCV infection. A number of other drugs with a broad spectrum of antiviral activity have been given to patients with hepatitis C. 4 To date, however, few convincing positive results have been obtained.HCV is a positive-stranded RNA virus with the genome size of approximately 9,400 bases and contains a large open reading frame encoding a precursor polyprotein of about 3,000 amino acids. [5][6][7][8] From their deduced amino acid sequence, HCV was shown to be related to pestiviruses and distantly related to flaviviruses. [8][9][10][11] Recent studies revealed that this polyprotein was cleaved into at least 9 mature proteins by host cellular signalases and viral coded proteinases. 12,13 However, because of the lack of an efficient in vitro cell culture system to grow the virus, little is known about the mechanisms of the replication of HCV. Synthesis of both replicative intermediate minus-strand HCV RNA and progeny positive-strand HCV RNA is thought to occur via an RNA-dependent RNA polymerase (RdRp) reaction. The nonstructural 5B (NS5B) protein of 65 kd is located at the C-terminal region of the HCV polyprotein and shares its sequence with those of other proteins of animal and plant viruses and bacteriophages possessing RdRp activity. 14,15

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Section: Methodsmentioning

confidence: 99%

Expression of Hepatitis C Virus Ns5b Protein: Characterization of Its Rna Polymerase Activity and Rna Binding

Ishii¹,

Tanaka²,

Yap³

et al. 1999

Hepatology

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“…The Sabin OPV strains contain attenuation mutations not only in their IRES elements but also in the encoded proteins (321,(344)(345)(346)(347). Some of them are known to readily revert in vaccinees or during subsequent transmission, resulting in the restoration of viral fitness (reviewed in references 312 and 313).…”

Section: Rehabilitation After Adverse Changes In Viral Proteinsmentioning

confidence: 99%

Emergency Services of Viral RNAs: Repair and Remodeling

Agol

Gmyl

2018

Microbiol Mol Biol Rev

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Reproduction of RNA viruses is typically error-prone due to the infidelity of their replicative machinery and the usual lack of proofreading mechanisms. The error rates may be close to those that kill the virus. Consequently, populations of RNA viruses are represented by heterogeneous sets of genomes with various levels of fitness. This is especially consequential when viruses encounter various bottlenecks and new infections are initiated by a single or few deviating genomes. Nevertheless, RNA viruses are able to maintain their identity by conservation of major functional elements. This conservatism stems from genetic robustness or mutational tolerance, which is largely due to the functional degeneracy of many protein and RNA elements as well as to negative selection. Another relevant mechanism is the capacity to restore fitness after genetic damages, also based on replicative infidelity. Conversely, error-prone replication is a major tool that ensures viral evolvability. The potential for changes in debilitated genomes is much higher in small populations, because in the absence of stronger competitors low-fit genomes have a choice of various trajectories to wander along fitness landscapes. Thus, low-fit populations are inherently unstable, and it may be said that to run ahead it is useful to stumble. In this report, focusing on picornaviruses and also considering data from other RNA viruses, we review the biological relevance and mechanisms of various alterations of viral RNA genomes as well as pathways and mechanisms of rehabilitation after loss of fitness. The relationships among mutational robustness, resilience, and evolvability of viral RNA genomes are discussed.

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“…Numerous studies show potential attenuating mutations for each serotype of OPV virus based on: (1) sequence comparisons between OPV virus strains and parental WPVs, (75,76) (2) sequence comparisons and/or neurovirulence testing in monkeys or mice of recombinant virus strains (i.e., swapping genetic segments between attenuated and neurovirulent strains) and/or site-directed mutants, (47,50,(77)(78)(79)(80)(81)(82)(83)(84) (3) OPV-related virus mutant strains after exposure to high temperature, (85) (4) OPV-related virus strains excreted by immunocompetent vaccine recipients without VAPP, (48,(86)(87)(88)(89) (5) OPV-related virus strains isolated from VAPP cases, (44)(45)(46)48,(90)(91)(92)(93)(94)(95)(96)(97)(98)(99) (6) strains isolated during cVDPV outbreaks, (15,57,100,101) (7) strains excreted by immunodeficient VDPV excretors, (102-106) (8) strains obtained during sequential passages after OPV administration in humans, (107) (9) strains obtained during sequential passages of OPV-related viruses in monkey tissues, (108) and (10) strains obtained from passages in cell culture. …”

Section: Attenuation and Reversionmentioning

confidence: 99%

“…These studies characterized mutations conferring attenuation of neurovirulence and/or increased temperature sensitivity, which correlates with attenuation, throughout the genome (e.g., nt 21 (5 -UTR), 189 (5 -UTR), 480 (5 -UTR), 935 (VP4-65), 2438 (VP3-225), 2795 (VP1-106), 2879 (VP1-134), 6203 (3D-73), 7441 (3 -UTR)) and identified the mutation at nt position 480 as one of the most critical, although the degree to which each potential attenuating mutation influences neurovirulence remains unclear. (77,81,82,97,111) Several studies show that some of the attenuating mutations of OPV1 revert in primary vaccine recipients over the period of excretion, although reversion at nt position 480, which can occur by direct reversion or by a compensating substitution at nt position 525, varies with respect to the proportion of primary vaccine recipients and time in different studies. (18,79,112) The virus strains isolated from type 1 VAPP cases also show the reversion of several attenuating mutations, most notably at nt position 480.…”

Section: Opv1mentioning

confidence: 99%

Oral Poliovirus Vaccine Evolution and Insights Relevant to Modeling the Risks of Circulating Vaccine‐Derived Polioviruses (cVDPVs)

Tebbens¹,

Pallansch

Kim³

et al. 2013

Risk Analysis

100

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The live, attenuated oral poliovirus vaccine (OPV) provides a powerful tool for controlling and stopping the transmission of wild polioviruses (WPVs), although the risks of vaccine-associated paralytic polio (VAPP) and circulating vaccine-derived poliovirus (cVDPV) outbreaks exist as long as OPV remains in use. Understanding the dynamics of cVDPV emergence and outbreaks as a function of population immunity and other risk factors may help to improve risk management and the development of strategies to respond to possible outbreaks. We performed a comprehensive review of the literature related to the process of OPV evolution and information available from actual experiences with cVDPV outbreaks. Only a relatively small fraction of poliovirus infections cause symptoms, which makes direct observation of the trajectory of OPV evolution within a population impractical and leads to significant uncertainty. Despite a large global surveillance system, the existing genetic sequence data largely provide information about transmitted virulent polioviruses that caused acute flaccid paralysis, and essentially no data track the changes that occur in OPV sequences as the viruses transmit largely asymptomatically through real populations with suboptimal immunity. We updated estimates of cVDPV risks based on actual experiences and identified the many limitations in the existing data on poliovirus transmission and immunity and OPV virus evolution that complicate modeling. Modelers should explore the space of potential model formulations and inputs consistent with the available evidence and future studies should seek to improve our understanding of the OPV virus evolution process to provide better information for policymakers working to manage cVDPV risks.

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Genetic analysis of the attenuation phenotype of poliovirus type 1

Cited by 180 publications

References 39 publications

Expression of Hepatitis C Virus Ns5b Protein: Characterization of Its Rna Polymerase Activity and Rna Binding

Expression of Hepatitis C Virus Ns5b Protein: Characterization of Its Rna Polymerase Activity and Rna Binding

Emergency Services of Viral RNAs: Repair and Remodeling

Oral Poliovirus Vaccine Evolution and Insights Relevant to Modeling the Risks of Circulating Vaccine‐Derived Polioviruses (cVDPVs)

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