Genetic Instability of RNA Viruses

Barr, John N.; Fearns, Rachel

doi:10.1016/b978-0-12-803309-8.00002-1

Cited by 28 publications

(30 citation statements)

References 100 publications

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“…The relationships between mutation rates, quasispecies, robustness, and evolvability of RNA viruses are discussed in detail in numerous publications (487,(515)(516)(517)(518)(519)(520)(521)(522)(523)(524)(525)(526). This problem is closely related to the emergence/reemergence of pathogenic viruses, which has recently become a hot topic (527)(528)(529)(530)(531)(532).…”

Section: Robustness Resilience and Evolvability Of Viral Rna Genomesmentioning

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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Section: Robustness Resilience and Evolvability Of Viral Rna Genomesmentioning

confidence: 99%

Emergency Services of Viral RNAs: Repair and Remodeling

Agol

Gmyl

2018

Microbiol Mol Biol Rev

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“…The CRISPR-powered COVID-19 testing of the target genes of SARS-CoV-2 ( Morales-Narváez and Dincer 2020 ) has been reported. Because viral RNAs are less stable during transport and storage than proteins such as antigens and antibodies ( Barr and Fearns 2016 ; Relova et al, 2018 ), false-negative RT-PCR results can arise due to improper collection of clinical specimens or poor handing of specimens during testing ( Li et al, 2020 ; Xie et al, 2020 ). For that reason, immunoassays represent reliable diagnostics for the detection of past infection, infection progress, and transmission dynamics.…”

Section: Introductionmentioning

confidence: 99%

A novel rapid detection for SARS-CoV-2 spike 1 antigens using human angiotensin converting enzyme 2 (ACE2)

Lee

Choi

Jung

et al. 2021

Biosensors and Bioelectronics

161

166

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a newly emerging human infectious disease. Because no specific antiviral drugs or vaccines are available to treat COVID-19, early diagnostics, isolation, and prevention are crucial for containing the outbreak. Molecular diagnostics using reverse transcription polymerase chain reaction (RT-PCR) are the current gold standard for detection. However, viral RNAs are much less stable during transport and storage than proteins such as antigens and antibodies. Consequently, false-negative RT-PCR results can occur due to inadequate collection of clinical specimens or poor handling of a specimen during testing. Although antigen immunoassays are stable diagnostics for detection of past infection, infection progress, and transmission dynamics, no matched antibody pair for immunoassay of SARS-CoV-2 antigens has yet been reported. In this study, we designed and developed a novel rapid detection method for SARS-CoV-2 spike 1 (S1) protein using the SARS-CoV-2 receptor ACE2, which can form matched pairs with commercially available antibodies. ACE2 and S1-mAb were paired with each other for capture and detection in a lateral flow immunoassay (LFIA) that did not cross-react with SARS-CoV Spike 1 or MERS-CoV Spike 1 protein. The SARS-CoV-2 S1 (<5 ng of recombinant proteins/reaction) was detected by the ACE2-based LFIA. The limit of detection of our ACE2-LFIA was 1.86 × 10 5 copies/mL in the clinical specimen of COVID-19 Patients without no cross-reactivity for nasal swabs from healthy subjects. This is the first study to detect SARS-CoV-2 S1 antigen using an LFIA with matched pair consisting of ACE2 and antibody. Our findings will be helpful to detect the S1 antigen of SARS-CoV-2 from COVID-19 patients.

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“…To achieve this, viruses modify antigenic epitopes on their proteins by continuously mutating their genomes. If the virus evolves in a stable environment with minimal selection, transition mutations are more frequent than the transversions [2]. Accumulation of deleterious mutations, which may include insertion, deletion, or substitution mutations, are filtered out through natural selection, either by reverting back to the ancestral state or by getting fixed with compensatory mutations that offset the effects of deleterious mutations while advantageous mutations persist [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

“…If the virus evolves in a stable environment with minimal selection, transition mutations are more frequent than the transversions [2]. Accumulation of deleterious mutations, which may include insertion, deletion, or substitution mutations, are filtered out through natural selection, either by reverting back to the ancestral state or by getting fixed with compensatory mutations that offset the effects of deleterious mutations while advantageous mutations persist [2][3][4][5]. Hence, digging deep into the type of mutations that occur may help in understanding how selection pressure might be acting on a novel virus [6].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of genomic diversity of SARS-CoV-2 in different geographic regions of India: an endeavour to classify Indian SARS-CoV-2 strains on the basis of co-existing mutations

et al. 2021

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Accumulation of mutations within the genome is the primary driving force in viral evolution within an endemic setting. This inherent feature often leads to altered virulence, infectivity and transmissibility, and antigenic shifts to escape host immunity, which might compromise the efficacy of vaccines and antiviral drugs. Therefore, we carried out a genome-wide analysis of circulating SARS-CoV-2 strains to detect the emergence of novel co-existing mutations and trace their geographical distribution within India. Comprehensive analysis of whole genome sequences of 837 Indian SARS-CoV-2 strains revealed the occurrence of 33 different mutations, 18 of which were unique to India. Novel mutations were observed in the S glycoprotein (6/33), NSP3 (5/33), RdRp/NSP12 (4/33), NSP2 (2/33), and N (1/33). Non-synonymous mutations were found to be 3.07 times more prevalent than synonymous mutations. We classified the Indian isolates into 22 groups based on their co-existing mutations. Phylogenetic analysis revealed that the representative strains of each group were divided into various sub-clades within their respective clades, based on the presence of unique co-existing mutations. The A2a clade was found to be dominant in India (71.34%), followed by A3 (23.29%) and B (5.36%), but a heterogeneous distribution was observed among various geographical regions. The A2a clade was highly predominant in East India, Western India, and Central India, whereas the A2a and A3 clades were nearly equal in prevalence in South and North India. This study highlights the divergent evolution of SARS-CoV-2 strains and co-circulation of multiple clades in India. Monitoring of the emerging mutations will pave the way for vaccine formulation and the design of antiviral drugs.

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Genetic Instability of RNA Viruses

Cited by 28 publications

References 100 publications

Emergency Services of Viral RNAs: Repair and Remodeling

Emergency Services of Viral RNAs: Repair and Remodeling

A novel rapid detection for SARS-CoV-2 spike 1 antigens using human angiotensin converting enzyme 2 (ACE2)

Comprehensive analysis of genomic diversity of SARS-CoV-2 in different geographic regions of India: an endeavour to classify Indian SARS-CoV-2 strains on the basis of co-existing mutations

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