Interferonstimulated Gene Screening Identifies Ccnd3 As A Host Restriction Factor Against Emerging Highpathogenic Bandaviruses Zhao Xu Zhenyu Jiang Kuan Feng Haiyan Zhang Chen Shi Fei Deng Hualin Wang Yunjia Ning by Zhao Xu & Zhenyu Jiang & Kuan Feng & Haiyan Zhang & Chen Shi & Fei Deng & Hualin Wang & Yun-jia Ning instant download after payment.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a representative high-pathogenic bandavirus (Bandavirus genus, Phenuiviridae family).Inducible expression of interferon-stimulated genes (ISGs) is the foundation ofhost antiviral defense; however, their roles in bandavirus infection remainelusive. Here, we identify over 200 ISGs potentially inhibiting or promotingbandaviral replication. With SFTSV as the main model, we further systematically uncover the notable antiviral role of one ISG, cyclin D3 (CCND3),against bandaviruses. SFTSV infection induces CCND3 up-regulation andcytoplasmic translocation. CCND3, in turn, inhibits the viral replication incultured cells and pathogenicity in vivo. The viral nucleoprotein (NP) is thetarget of CCND3. By its CN domain, CCND3 interacts with NP’s “head” region inan RNA-independent manner, suppressing the ribonucleoprotein (RNP)replication machinery activity. Furthermore, consistent with interactioninterface mapping and structural modeling analyses, the CCND3-NP interaction blocks NP multimerization, NP-RNA binding, and NP association with viralpolymerase, that is, the NP activities essential to RNP construction and functioning. Conversely, the viral nonstructural protein, NSs, can partially antagonize CCND3 by attenuating its induction and promoting autophagicdegradation. These findings provide new insights into bandavirus-host interactions and arms race, advancing the understanding of bandavirus infectionand probably informing antiviral therapeutic development.