Flavivirus NS1 possesses NTPase and RNA helix unwinding activities
4 affiliations
- 1State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
- 2University of Chinese Academy of Sciences, Beijing 100049, China
- 3University of Science and Technology of China, Hefei 230026, China
- 4Wuhan Jinyintan Hospital, Wuhan 430023, China
Abstract
Flaviviruses are a group of arthropod-borne positive-sense RNA viruses, including Zika virus (ZIKV), dengue virus 2 (DENV2) and Japanese encephalitis virus (JEV). For RNA viruses, RNA helicases play critical roles in viral replication by unwinding double-stranded RNA intermediates generated in viral life cycles by remodeling viral RNA structures. Here, we report that NS1 proteins from ZIKV, DENV2 and JEV, possesse NTPase and RNA helix unwinding activities. ZIKV NS1 unwinds dsRNA in an NTP-dependent manner with 5′ → 3′ directionality, and its unwinding activity is broad-spectrum, targeting dsRNA, dsDNA and RNA/DNA hybrids. Moreover, both DENV2 and JEV NS1 also display NTPase and helicase activities, but they differ in substrate preference and directionality: JEV NS1 unwinds in the 5′ → 3′ direction like ZIKV NS1, whereas DENV2 NS1 unwinds only shorter duplexes and shows 3′ → 5′ directionality. Mutagenesis identified the basic residue at position 211 (arginine in ZIKV, lysine in DENV2/JEV) as critical for the unwinding activity of ZIKV and JEV NS1, but dispensable for DENV2 NS1. These findings indicate that flavivirus NS1 represents a previously unrecognized non-canonical RNA helicase, suggesting that NS1 may have the capacity to participate in RNA remodeling processes.
Related
- Extract of Cinnamomum cassia L. possesses an inhibitor of pancreatic lipase and α-glucosidase that acts as a potential antidiabesity agent
- Seroprevalence of Japanese encephalitis virus and other flavivirus-specific antibodies among Australian blood donors following a novel epidemic spread of Japanese encephalitis virus: a cross-sectional study
- The α-helix-facilitating amino acid sequence EAAAK dramatically increases the antiviral activity of SARS-CoV-2 fusion-inhibitory peptides via the endosome fusion pathway
- Development and evaluation of a practical teaching model for medical laboratory interns based on the "quality-safety-patient-centered" triple helix framework.
- Effect of red and infrared light on the modulation of microglial activities
BibTeX
@article{shu2026flavivirus,
title = {{Flavivirus NS1 possesses NTPase and RNA helix unwinding activities}},
author = {Ting Shu and Mengyu Hu and Yiyang Li and Mengge Han and Xingyue Wang and Qi Cheng and Xiqiu Xu and Yang Qiu and Xi Zhou},
journal = {Virologica Sinica},
year = {2026},
month = sep,
doi = {10.1016/j.virs.2026.09.007},
url = {https://doi.org/10.1016/j.virs.2026.09.007},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Flavivirus NS1 possesses NTPase and RNA helix unwinding activities
AU - Ting Shu
AU - Mengyu Hu
AU - Yiyang Li
AU - Mengge Han
AU - Xingyue Wang
AU - Qi Cheng
AU - Xiqiu Xu
AU - Yang Qiu
AU - Xi Zhou
PY - 2026
DA - 2026/09/17
JO - Virologica Sinica
DO - 10.1016/j.virs.2026.09.007
UR - https://doi.org/10.1016/j.virs.2026.09.007
AB - Flaviviruses are a group of arthropod-borne positive-sense RNA viruses, including Zika virus (ZIKV), dengue virus 2 (DENV2) and Japanese encephalitis virus (JEV). For RNA viruses, RNA helicases play critical roles in viral replication by unwinding double-stranded RNA intermediates generated in viral life cycles by remodeling viral RNA structures. Here, we report that NS1 proteins from ZIKV, DENV2 and JEV, possesse NTPase and RNA helix unwinding activities. ZIKV NS1 unwinds dsRNA in an NTP-dependent manner with 5′ → 3′ directionality, and its unwinding activity is broad-spectrum, targeting dsRNA, dsDNA and RNA/DNA hybrids. Moreover, both DENV2 and JEV NS1 also display NTPase and helicase activities, but they differ in substrate preference and directionality: JEV NS1 unwinds in the 5′ → 3′ direction like ZIKV NS1, whereas DENV2 NS1 unwinds only shorter duplexes and shows 3′ → 5′ directionality. Mutagenesis identified the basic residue at position 211 (arginine in ZIKV, lysine in DENV2/JEV) as critical for the unwinding activity of ZIKV and JEV NS1, but dispensable for DENV2 NS1. These findings indicate that flavivirus NS1 represents a previously unrecognized non-canonical RNA helicase, suggesting that NS1 may have the capacity to participate in RNA remodeling processes.
SN - 1674-0769
SN - 1995-820X
ER -