ArticlePLoS pathogens2019
Multiple roles of the non-structural protein 3 (nsP3) alphavirus unique domain (AUD) during Chikungunya virus genome replication and transcription.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- The life cycle of the alphaviruses: From an antiviral perspective.Antiviral research · 2023Pooled it
- A randomized, double-blinded Phase 3 study to demonstrate lot-to-lot consistency and to confirm immunogenicity and safety of the live-attenuated chikungunya virus vaccine candidate VLA1553 in healthy adults†.Journal of travel medicine · 2024Trial
- Chikungunya virus nsP2: Insights into viral replication, pathogenesis, and therapeutic targeting.Virulence · 2026Review
- Recent progress in anti-Chikungunya virus drug discovery: Focus on the viral life cycle and direct-acting antivirals.Virologica Sinica · 2026Review
- Alphavirus nsP3 as a multifunctional orchestrator of virus-host interplay.Journal of virology · 2026Review
- Alphavirus replicase and regulatory RNA elements in host interactions and viral vector engineering.Journal of virology · 2026Review
- Review
- The cross-city mobility patterns and incubation period of the early-stage chikungunya fever outbreak in Guangdong Province, China, in 2025.PLoS neglected tropical diseases · 2026Article
- The SMARCA4-TMEM47 axis plays an essential role in chikungunya virus RNA replication.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Biocompatible ligand balancing in transition metal coordination enables benign in-cell protein arylation.Nature chemistry · 2026Article
- Chikungunya in 2025: Comprehensive Insights into Virology, Diagnostics, Vaccines, and Antiviral Therapies.Viruses · 2026Review
- Phenol and chromone compounds forPharmaceutical science advances · 2025Article
- Trans-complementation of chikungunya virus replicase mutants reveals alphavirus replication complexity and supports antiviral tool development.PLoS pathogens · 2025Article
- The impact of variations in the chikungunya genome on the clinical manifestations and transmission of the disease.Journal of family medicine and primary care · 2025Review
- Article
- Minimal polymerase-containing precursor required for Chikungunya virus RNA synthesis.bioRxiv : the preprint server for biology · 2025Article
- Optimum level of NEDD4 and its interaction with nsP3 are crucial to facilitate efficient Chikungunya virus (CHIKV) infection.The Journal of general virology · 2025Article
- Live Imaging and Interactome Analysis of Zika and Chikungunya Viral RNAs Via Dual-Action Aptamer Tag.Research square · 2025Article
- The Re-emergence of Chikungunya in Sri Lanka: A Genomic investigation.medRxiv : the preprint server for health sciences · 2025Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Chikungunya virus (CHIKV) is a re-emerging Alphavirus causing fever, joint pain, skin rash, arthralgia, and occasionally death. Antiviral therapies and/or effective vaccines are urgently required. CHIKV biology is poorly understood, in particular the functions of the non-structural protein 3 (nsP3). Here we present the results of a mutagenic analysis of the alphavirus unique domain (AUD) of nsP3. Informed by the structure of the Sindbis virus AUD and an alignment of amino acid sequences of multiple alphaviruses, a series of mutations in the AUD were generated in a CHIKV sub-genomic replicon. This analysis revealed an essential role for the AUD in CHIKV RNA replication, with mutants exhibiting species- and cell-type specific phenotypes. To test if the AUD played a role in other stages of the virus lifecycle, the mutants were analysed in the context of infectious CHIKV. This analysis indicated that the AUD was also required for virus assembly. In particular, one mutant (P247A/V248A) exhibited a dramatic reduction in production of infectious virus. This phenotype was shown to be due to a block in transcription of the subgenomic RNA leading to reduced synthesis of the structural proteins and a concomitant reduction in virus production. This phenotype could be further explained by both a reduction in the binding of the P247A/V248A mutant nsP3 to viral genomic RNA in vivo, and the reduced affinity of the mutant AUD for the subgenomic promoter RNA in vitro. We propose that the AUD is a pleiotropic protein domain, with multiple functions during CHIKV RNA synthesis.
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