lncRNA Sensing of a Viral Suppressor of RNAi Activates Non-canonical Innate Immune Signaling in Drosophila

Liqin Zhang; Wen Xu; Xinlei Gao; Wenjie Li; Shuishui Qi; Dongyang Guo; Olugbenga Emmanuel Ajayi; Shou-Wei Ding; Qingfa Wu

doi:10.1016/j.chom.2019.12.006

lncRNA Sensing of a Viral Suppressor of RNAi Activates Non-canonical Innate Immune Signaling in Drosophila

Cell Host Microbe. 2020 Jan 8;27(1):115-128.e8. doi: 10.1016/j.chom.2019.12.006.

Authors

Liqin Zhang¹, Wen Xu¹, Xinlei Gao¹, Wenjie Li¹, Shuishui Qi¹, Dongyang Guo¹, Olugbenga Emmanuel Ajayi¹, Shou-Wei Ding², Qingfa Wu³

Affiliations

¹ Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
² Department of Microbiology and Plant Pathology, Institute for Integrative Genome Biology, University of California, Riverside CA, USA.
³ Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: wuqf@ustc.edu.cn.

PMID: 31917956
DOI: 10.1016/j.chom.2019.12.006

Abstract

Antiviral immunity in insects is mediated by the RNA interference (RNAi) pathway. Viruses evade antiviral RNAi by expressing virulence factors known as viral suppressors of RNAi (VSR). Here, we report the identification of VINR, a Drosophila VSR-interacting long non-coding (lnc) RNA that activates non-canonical innate immune signaling upon detection of the dsRNA-binding VSR of Drosophila C virus (DCV). VINR is required for the induction of antimicrobial peptide (AMP) genes but dispensable for antiviral RNAi. VINR functions by preventing the ubiquitin proteasome-dependent degradation of Cactin, a coiled-coil and arginine-serine-rich domain-containing protein that regulates a non-cannonical antimicrobial pathway for AMP induction. CRISPR-Cas9 knockout of VINR in Drosophila cells enhances DCV replication independently of antiviral RNAi, and VINR-knockout adult flies exhibit enhanced disease susceptibility to DCV and bacteria. Our findings reveal a counter counter-defense strategy activated by a lncRNA in response to the viral suppression of the primary antiviral RNAi immunity.

Keywords: Cactin; Deaf1; Drosophila; IMD pathway; RNAi immunity; Toll pathway; counter counter-defense; lncRNA; viral suppressors of RNAi; virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antimicrobial Cationic Peptides / genetics
Antimicrobial Cationic Peptides / metabolism
CRISPR-Cas Systems
Carrier Proteins / metabolism*
Dicistroviridae / genetics
Dicistroviridae / immunology*
Dicistroviridae / pathogenicity
Drosophila Proteins / metabolism*
Drosophila melanogaster / genetics
Drosophila melanogaster / immunology*
Gene Knockdown Techniques
Immunity, Innate
RNA Interference / immunology
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / immunology
RNA, Long Noncoding* / metabolism
Signal Transduction
Viral Proteins / metabolism
Virulence Factors / metabolism

Substances

Antimicrobial Cationic Peptides
Carrier Proteins
Drosophila Proteins
RNA, Long Noncoding
Viral Proteins
Virulence Factors
cactin protein, Drosophila

Supplementary concepts

Drosophila C virus