Synonymous Virus Genome Recoding as a Tool to Impact Viral Fitness

Martı́nez, Miguel Ángel; Jordan-Paiz, Ana; Franco, Sandra; Nevot, María

doi:10.1016/j.tim.2015.11.002

Cited by 76 publications

(72 citation statements)

References 72 publications

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“…But most of the focuses are on human viral pathogens, which include influenza virus (Mueller et al., ), poliovirus (Sanders, Edo‐Matas, Papic, Schuitemaker, & Custers, ), Chikungunya virus (Powers, ) and HIV (Martrus, Nevot, Andres, Clotet, & Martinez, ). Among the approaches to construct attenuated live synthetic viruses include genome‐scale changes in codon‐pair bias (Mueller et al., ) and codon de‐optimization (Evenson et al., ; Martínez, Jordan‐Paiz, Franco, & Nevot, ). These approaches recode the virus genome synonymously that subsequently impact the viral fitness, which has been proven to be efficient in laboratory animal model, thus suggesting the potential application of these approaches as alternative vaccine strategies against viral infection in aquatic animals.…”

Section: Future Perspectivementioning

confidence: 99%

Molecular biology of Macrobrachium rosenbergii nodavirus infection in giant freshwater prawn

Low

Yusoff²,

Kuppusamy³

et al. 2018

Journal of Fish Diseases

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Macrobrachium rosenbergii nodavirus (MrNV) has been threatening the giant freshwater prawn aquaculture since 1997, causing white tail disease in the prawn species that leads to 100% lethality of the infected postlarvae. Comprehension of the viral infectivity and pathogenesis at molecular biology level has recently resolved the viral capsid protein and evidenced the significant difference in the viral structural protein compared to other nodaviruses that infect fish and insect. Cumulative researches have remarked the proposal to assert MrNV as a member of new genus, gammanodavirus to the Nodaviridae family. The significance of molecular biology in MrNV infection is being highlighted in this current review, revolving the viral life cycle from virus binding and entry into host, virus replication in host cell, to virus assembly and release. The current review also highlights the emerging aptamers technology that is also known as synthetic antibody, its application in disease diagnosis, and its prophylactic and therapeutic properties. The future perspective of synthetic virology technology in understanding viral pathogenesis, as well as its potential in viral vaccine development, is also discussed.

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Section: Future Perspectivementioning

confidence: 99%

Molecular biology of Macrobrachium rosenbergii nodavirus infection in giant freshwater prawn

Low

Yusoff²,

Kuppusamy³

et al. 2018

Journal of Fish Diseases

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show abstract

“…The main strategies for attenuation by synonymous genome recoding are codon deoptimization (CD), codon pair deoptimization (CPD), and increasing the dinucleotide CpG and UpA content (which is usually the result of CD and CPD) (2).…”

mentioning

confidence: 99%

Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure

Nouën

McCarty

Brown

et al. 2017

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

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Recoding viral genomes by numerous synonymous but suboptimal substitutions provides live attenuated vaccine candidates. These vaccine candidates should have a low risk of deattenuation because of the many changes involved. However, their genetic stability under selective pressure is largely unknown. We evaluated phenotypic reversion of deoptimized human respiratory syncytial virus (RSV) vaccine candidates in the context of strong selective pressure. Codon pair deoptimized (CPD) versions of RSV were attenuated and temperature-sensitive. During serial passage at progressively increasing temperature, a CPD RSV containing 2,692 synonymous mutations in 9 of 11 ORFs did not lose temperature sensitivity, remained genetically stable, and was restricted at temperatures of 34°C/35°C and above. However, a CPD RSV containing 1,378 synonymous mutations solely in the polymerase L ORF quickly lost substantial attenuation. Comprehensive sequence analysis of virus populations identified many different potentially deattenuating mutations in the L ORF as well as, surprisingly, many appearing in other ORFs. Phenotypic analysis revealed that either of two competing mutations in the virus transcription antitermination factor M2-1, outside of the CPD area, substantially reversed defective transcription of the CPD L gene and substantially restored virus fitness in vitro and in case of one of these two mutations, also in vivo. Paradoxically, the introduction into Min L of one mutation each in the M2-1, N, P, and L proteins resulted in a virus with increased attenuation in vivo but increased immunogenicity. Thus, in addition to providing insights on the adaptability of genome-scale deoptimized RNA viruses, stability studies can yield improved synthetic RNA virus vaccine candidates.negative-strand RNA virus | respiratory syncytial virus | live attenuated vaccine | codon pair deoptimization | genetic stability T he availability and affordability of large-scale custom DNA synthesis opened the new field of synthetic biology (1). The combined approach of sequence design and synthetic biology allows the generation of DNA molecules with extensive targeted modifications. Synonymous genome recoding, in which one or more ORFs of a microbial pathogen are modified at the nucleotide level without affecting amino acid coding, currently is being widely evaluated to reduce pathogen fitness and create potential live attenuated vaccines, particularly for RNA viruses (reviewed in ref.2) (3-7). The main strategies for attenuation by synonymous genome recoding are codon deoptimization (CD), codon pair deoptimization (CPD), and increasing the dinucleotide CpG and UpA content (which is usually the result of CD and CPD) (2).The mechanisms of attenuation by these strategies are currently under intensive research. It has been suggested that the primary effect of CD and CPD is to reduce translation efficiency of pathogen mRNAs, thereby providing attenuation (8). Effects on mRNA stability also can be a factor (9). In addition, recent studies suggested that codon pa...

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“…Evidence to the contrary has been obtained with viruses and cells, including mutations in the human genome that may affect enhancer functions (Hirsch and Birnbaum, 2015), mRNA folding (Faure et al, 2017;Mittal et al, 2018), and microRNA targeting (Brest et al, 2011), among other processes (Novella, 2004;Novella et al, 2004;Parmley et al, 2006;Hamano et al, 2007;Resch et al, 2007;Lafforgue et al, 2011;Nevot et al, 2011Nevot et al, , 2018Supek, 2016). There are several mechanisms by which synonymous mutations can affect virus behavior: alteration of cis-acting regulatory elements in viral genomes, decrease of the stability of duplex structures within the RNA genome or between viral sequences and miRNAs or siRNAs, or changes of viral gene expression [splicing precision or translation fidelity through the modification of RNA-RNA or RNA-protein interactions; reviewed in (Martínez et al, 2016)].…”

Section: Types and Effects Of Mutationsmentioning

confidence: 99%

Molecular basis of genetic variation of viruses

Domingo

2020

Virus as Populations

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Synonymous Virus Genome Recoding as a Tool to Impact Viral Fitness

Cited by 76 publications

References 72 publications

Molecular biology of Macrobrachium rosenbergii nodavirus infection in giant freshwater prawn

Molecular biology of Macrobrachium rosenbergii nodavirus infection in giant freshwater prawn

Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure

Molecular basis of genetic variation of viruses

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