A replication-defective Chikungunya Virus platform for high-throughput drug screening and diagnostics
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that poses a significant global health threat. Although vaccines have recently been approved, the requirement for Biosafety Level 3 (BSL-3) containment substantially impedes therapeutic and diagnostic development for CHIKV. Here, we engineered an RNA replication-defective CHIKV (CHIKV-ΔnsP4) via trans-complementation, wherein the deleted nsP4 gene product is supplied in trans. CHIKV-ΔnsP4 replicates exclusively in nsP4-expressing cells, completing a full infectious cycle, while exhibiting no detectable replication in naïve cells. Consistent with this, CHIKV-ΔnsP4 demonstrated high attenuation in animal models. Building upon this platform, we generated an mCherry-expressing RNA replication-defective reporter virus, which enabled high-content antiviral screening and serological diagnostics. Collectively, this study establishes the RNA replication-defective strategy as a safe and effective platform for CHIKV research.
Authors
- Cheng‐Lin Deng (ORCID: https://orcid.org/0000-0003-3469-2263)
- Jie Huang (ORCID: https://orcid.org/0000-0002-3917-912X)
- Bo Zhang (ORCID: https://orcid.org/0000-0002-8895-3679)
- Zherui Zhang
- Yanan Zhang
- Yue Li
- Jiaqi Li
- Qiuyan Zhang
- Jing Wang
Institutions
- University of Science and Technology of China (CN)
- Chinese Academy of Sciences (CN)
- Wuhan Institute of Virology (CN)
- Anhui Provincial Center for Disease Control and Prevention (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Emerging Microbes & Infections
- Published
- 2026-11-10
- DOI
- https://doi.org/10.1080/22221751.2026.2761721
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 0.00