Related Experiment Video
Updated: Feb 4, 2026

RNAi Screening for Host Factors Involved in Vaccinia Virus Infection using Drosophila Cells
Published on: August 25, 2010
A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability
Arabinda Nayak1, Dong Young Kim2, Michael J Trnka3
1Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94158, USA; Department of Biology and Genetics, Stanford University, Stanford, CA 94305, USA.
Abstract:
The dicistrovirus, Cricket paralysis virus (CrPV) encodes an RNA interference (RNAi) suppressor, 1A, which modulates viral virulence. Using the Drosophila model, we combined structural, biochemical, and virological approaches to elucidate the strategies by which CrPV-1A restricts RNAi immunity. The atomic resolution structure of CrPV-1A uncovered a flexible loop that interacts with Argonaute 2 (Ago-2), thereby inhibiting Ago-2 endonuclease-dependent immunity. Mutations disrupting Ago-2 binding attenuates viral pathogenesis in wild-type but not Ago-2-deficient flies. CrPV-1A also contains a BC-box motif that enables the virus to hijack a host Cul2-Rbx1-EloBC ubiquitin ligase complex, which promotes Ago-2 degradation and virus replication. Our study uncovers a viral-based dual regulatory program that restricts antiviral immunity by direct interaction with and modulation of host proteins. While the direct inhibition of Ago-2 activity provides an efficient mechanism to establish infection, the recruitment of a ubiquitin ligase complex enables CrPV-1A to amplify Ago-2 inactivation to restrict further antiviral RNAi immunity.
Related Concept Videos
Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Regulated Protein Degradation
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
Covalently Linked Protein Regulators
Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
Active versus Passive Immunity
Active Immunity
Active immunity refers to the resistance one develops...

