NUP98 regulates orthoflavivirus replication through interaction with vRNA and can be targeted for antiviral purposes.
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Peters MBA, Lindqvist R, Madhu P, Lundmark R, Ivarsson Y, Överby AK
Nucleic Acids Res. 54 (3) - [2026-01-22; online 2026-01-27]
The nuclear pore complex (NPC) is composed of multiple nucleoporins (NUPs) and enables the exchange of RNA and proteins between the nucleus and cytoplasm. NUP98 is one of the major components of the NPC, being involved in the RNA export pathway by interacting with several transport factors. Previous studies have suggested both proviral and antiviral functions of NUP98 in viral infection, yet little is known about its function in orthoflavivirus infection. In this study we show that NUP98 is a proviral cellular protein that is recruited to the cytoplasm during orthoflavivirus infection. We observe that NUP98 is found specifically in the vicinity of the replication vesicles during infections with tick-borne encephalitis virus, Japanese encephalitis virus, and yellow fever virus. Furthermore, using surface plasmon resonance, cross-link immunoprecipitation, and cross-link immunoprecipitation-sequencing we observe that the C-terminal domain of NUP98 directly interacts with a conserved site of the viral RNA (vRNA) in the E coding region promoting viral replication. We identified a peptide that binds to NUP98 that is antivirally active against several orthoflaviviruses by outcompeting the binding between NUP98 and vRNA, making NUP98 an attractive target for antiviral development.
NGI Stockholm (Genomics Production) [Service]
National Genomics Infrastructure [Service]
PubMed 41591840
DOI 10.1093/nar/gkag027
Crossref 10.1093/nar/gkag027
pmc: PMC12839527
pii: 8442274