Downregulating Viral Gene Expression: Codon Usage Bias Manipulation for the Generation of Novel Influenza A Virus Vaccines

Baker, Steven F.; Nogales, Aitor; Martínez-Sobrido, Luis

doi:10.2217/fvl.15.31

Cited by 34 publications

(43 citation statements)

References 93 publications

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“…Secondly, the information of genome-wide codon usage pattern of SARS-CoV-2 may have potential value for developing coronavirus vaccines to combat this pandemic disease. The information on codon usage by SARS-CoV-2 may pave the way to design strategies such as codon deoptimization [19][20][21], the use of the least preferred codons to modify the SARS-CoV-2 genome to reduce virulence for the development of a safe and effective vaccine. This strategy has several advantages.…”

Section: Nucleotide Composition Analysis (Supplementarymentioning

confidence: 99%

Characterization of Codon Usage Pattern in SARS-CoV-2

Hou¹

2020

Preprint

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The outbreak of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed significant threats to international health. The genetic traits as well as evolutionary processes in this novel coronavirus are not fully characterized, and their roles in viral pathogenesis are yet largely unknown. To get a better picture of the codon architecture of this newly emerging coronavirus, in this study we perform bioinformatic analysis, based on publicly available nucleotide sequences of SARS-CoV-2 along with those of other members of human coronaviruses as well as non-human coronaviruses in different hosts, to take a snapshot of the genome-wide codon usage pattern of SARS-CoV-2 and uncover that all over-represented codons end with A/U and this newly emerging coronavirus has a relatively low codon usage bias, which is shaped by both mutation pressure and natural selection. Additionally, there is slight variation in the codon usage pattern among the SARS-CoV-2 isolates from different geo-locations. Furthermore, the overall codon usage pattern of SARS-CoV-2 is generally similar to that of its phylogenetic relatives among non-human betacoronaviruses such as RaTG13. Taken together, we comprehensively analyze the characteristics of codon usage pattern in SARS-CoV-2 via bioinformatic approaches. The information from this research may not only be helpful to get new insights into the evolution of SARS-CoV-2, but also have potential value for developing coronavirus vaccines.

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Section: Nucleotide Composition Analysis (Supplementarymentioning

confidence: 99%

Characterization of Codon Usage Pattern in SARS-CoV-2

Hou¹

2020

Preprint

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“…Plasmid-based reverse genetics to generate recombinant influenza viruses (Fodor et al, 1999;Neumann et al, 1999) has significantly contributed to a better understanding of the biology of these important human respiratory pathogens (Engelhardt, 2013;Jackson et al, 2011a), for the identification and characterization of antivirals (Baker et al, 2014;Ozawa and Kawaoka, 2011;Roberts et al, 2015), and for the development of alternative influenza vaccines (Baker et al, 2015a;Nogales et al, 2014a;Subbarao and Katz, 2004). Reverse genetics have allowed for the generation of replication-competent IAVs expressing reporter genes as novel powerful tools to track viral infections without the requirement of secondary methodologies to detect viral-infected cells (Eckert et al, 2014;Fiege and Langlois, 2015;Fukuyama et al, 2015;Kittel et al, 2004;Manicassamy et al, 2010;Nogales et al, 2014a;Pan et al, 2013;Perez et al, 2013;Reuther et al, 2015;Tran et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Replication-competent fluorescent-expressing influenza B virus

et al. 2016

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Influenza B viruses (IBVs) cause annual outbreaks of respiratory illness in humans and are increasingly recognized as a major cause of influenza-associated morbidity and mortality. Studying influenza viruses requires the use of secondary methodologies to identify virus-infected cells. To this end, replication-competent influenza A viruses (IAVs) expressing easily traceable fluorescent proteins have been recently developed. In contrast, similar approaches for IBV are mostly lacking. In this report, we describe the generation and characterization of replication-competent influenza B/Brisbane/60/2008 viruses expressing fluorescent mCherry or GFP fused to the C-terminal of the viral non-structural 1 (NS1) protein. Fluorescent-expressing IBVs display similar growth kinetics and plaque phenotype to wild-type IBV, while fluorescent protein expression allows for the easy identification of virus-infected cells. Without the need of secondary approaches to monitor viral infection, fluorescent-expressing IBVs represent an ideal approach to study the biology of IBV and an excellent platform for the rapid identification and characterization of antiviral therapeutics or neutralizing antibodies using high-throughput screening approaches. Lastly, fluorescent-expressing IBVs can be combined with the recently described reporter-expressing IAVs for the identification of novel therapeutics to combat these two important human respiratory pathogens.

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“…IAV contains a single-stranded negative-sense viral (v)RNA genome consisting of eight segments that are encapsidated within enveloped spherical or filamentous particles ( Figure 1 A) [ 18 ]. The IAV genome encodes up to 16 different viral proteins using multiple strategies such as overlapping open reading frames (ORFs), alteRNAtive splicing and frameshift mechanisms [ 18 , 58 , 59 , 60 ]. Each of the vRNA segments are flanked at both termini by non-coding regions (NCRs) that serve as polymerase promoters for viral genome replication and gene transcription ( Figure 1 B).…”

Section: Iav Genome Organization Virion Structure and Life Cyclementioning

confidence: 99%

Temperature Sensitive Mutations in Influenza A Viral Ribonucleoprotein Complex Responsible for the Attenuation of the Live Attenuated Influenza Vaccine

Martínez-Sobrido

Peersen

Nogales

2018

Viruses

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Live attenuated influenza vaccines (LAIV) have prevented morbidity and mortality associated with influenza viral infections for many years and represent the best therapeutic option to protect against influenza viral infections in humans. However, the development of LAIV has traditionally relied on empirical methods, such as the adaptation of viruses to replicate at low temperatures. These approaches require an extensive investment of time and resources before identifying potential vaccine candidates that can be safely implemented as LAIV to protect humans. In addition, the mechanism of attenuation of these vaccines is poorly understood in some cases. Importantly, LAIV are more efficacious than inactivated vaccines because their ability to mount efficient innate and adaptive humoral and cellular immune responses. Therefore, the design of potential LAIV based on known properties of viral proteins appears to be a highly appropriate option for the treatment of influenza viral infections. For that, the viral RNA synthesis machinery has been a research focus to identify key amino acid substitutions that can lead to viral attenuation and their use in safe, immunogenic, and protective LAIV. In this review, we discuss the potential to manipulate the influenza viral RNA-dependent RNA polymerase (RdRp) complex to generate attenuated forms of the virus that can be used as LAIV for the treatment of influenza viral infections, one of the current and most effective prophylactic options for the control of influenza in humans.

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Downregulating Viral Gene Expression: Codon Usage Bias Manipulation for the Generation of Novel Influenza A Virus Vaccines

Cited by 34 publications

References 93 publications

Characterization of Codon Usage Pattern in SARS-CoV-2

Characterization of Codon Usage Pattern in SARS-CoV-2

Replication-competent fluorescent-expressing influenza B virus

Temperature Sensitive Mutations in Influenza A Viral Ribonucleoprotein Complex Responsible for the Attenuation of the Live Attenuated Influenza Vaccine

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