Mutation of the N-Terminal Region of Chikungunya Virus Capsid Protein: Implications for Vaccine Design

@article{Taylor2017MutationOT,
  title={Mutation of the N-Terminal Region of Chikungunya Virus Capsid Protein: Implications for Vaccine Design},
  author={Adam Taylor and Xiang Liu and Ali Zaid and Lucas Y. H. Goh and J. Hobson-Peters and R. Hall and A. Merits and S. Mahalingam},
  journal={mBio},
  year={2017},
  volume={8}
}
Mosquito-transmitted chikungunya virus (CHIKV) is an arthritogenic alphavirus of the Togaviridae family responsible for frequent outbreaks of arthritic disease in humans. [...] Key Result Mutation of the NoLS by site-directed mutagenesis reduced efficiency of nuclear import of CHIKV capsid protein. In the virus, mutation of the capsid protein NoLS (CHIKV-NoLS) attenuated replication in mammalian and mosquito cells, producing a small-plaque phenotype.Expand
Mutation of a Conserved Nuclear Export Sequence in Chikungunya Virus Capsid Protein Disrupts Host Cell Nuclear Import
TLDR
In contrast to encephalitic alphaviruses, CHIKV capsidprotein did not inhibit host nuclear import; however, mutating the NES of capsid protein (∆NES) blocked host protein access to the nucleus, warranting further investigation. Expand
Attenuation and Stability of CHIKV-NoLS, a Live-Attenuated Chikungunya Virus Vaccine Candidate
TLDR
To examine the stability of attenuation and suitability as a vaccine, the plaque phenotype and replication kinetics of CHIKV-NoLS were determined following extended in vitro passage and the average plaque size remained notably smaller than CHikV-WT after extended passage and attenuated replication was maintained. Expand
Role of nuclear localization signals in the DNA delivery function of Chikungunya virus capsid protein.
TLDR
The findings suggest that the capsid of CHikV might influence cellular trafficking in the infected cell via non-specific interactions and indicates the significance of NLS sequences in the multifunctionality of CHIKV capsid protein. Expand
Liposomal Delivery of the RNA Genome of a Live-Attenuated Chikungunya Virus Vaccine Candidate Provides Local, but Not Systemic Protection After One Dose
TLDR
Results suggest that in the presence of low CHIKV-specific neutralizing antibody levels, local inflammatory responses, likely brought on by liposome adjuvants, have a role in the protection of Chikungunya virus-induced footpad swelling in the ipsilateral foot of mice inoculated withliposome-delivered ChikV-NoLS RNA. Expand
Infectious Chikungunya Virus (CHIKV) with a Complete Capsid Deletion: a New Approach for a CHIKV Vaccine
TLDR
A novel live attenuated vaccine candidate for CHIKV lacking the entire capsid gene, ΔC-CHIKV, was developed and demonstrated to be genetically stable, highly attenuated, immunogenic, and able to confer complete protection against lethal Chikungunya virus challenge after a single dose of immunization. Expand
The effect of amantadine on an ion channel protein from Chikungunya virus
TLDR
This study provides crucial mechanistic insights into the functionality of 6K during CHIKV-host interaction and suggests that 6K is a potential therapeutic drug target, with amantadine and its derivatives being strong candidates for further development. Expand
The Interplay of Viral and Host Factors in Chikungunya Virus Infection: Targets for Antiviral Strategies
TLDR
There is a pressing need for an in-depth understanding of the interaction between the host environment and CHIKV in order to generate potential therapeutics against this debilitating virus. Expand
Targeting Chikungunya virus by computational approaches: from viral biology to the development of therapeutic strategies
TLDR
It is reviewed how computational tools have provided insights on CHIKV proteins and the advances in the development of potential and novel antiviral drugs and the design of new anti-CHIKV agents. Expand
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TLDR
There is an urgent need to better understand the virus–host interactions that will facilitate antiviral drug development and thus reduce the global burden of infections caused by arboviruses. Expand
Arthritogenic Alphavirus Capsid Protein
TLDR
This review describes studies that have used capsid protein to develop novel arthritogenic alphavirus therapeutic and diagnostic strategies, and summarizes the function of arthritic alphvirus capsidprotein. Expand
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