Research

Life Sciences & Biotechnology

Title :

Characterization of molecular interaction between influenza virus Nonstructural protein-1 (NS1) and viral Ribonucleoprotein complex (RNP) and elucidating the role of this interaction in regulating viral RNA synthesis and virus replication.

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Arindam Mondal, Indian Institute Of Technology (IIT) Kharagpur, West Bengal

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Equipments :

Details

Executive Summary :

The successful completion of the RNA virus life cycle relies on two key events: transcription and replication of the viral RNA genome to produce progeny virion particles and suppression of host antiviral response through specific recruitment of viral antigens. Influenza is a negative sense RNA virus that utilizes ribonucleoprotein complexes (RNPs) and non-structural protein 1 (NS1) to antagonize host immune response. Previous reports suggest that NS1 protein directly interacts with viral nucleoprotein NP, which is the major constituent of RNPs, and plays an atypical role in directly promoting influenza virus RNA synthesis. This project aims to characterize the NS1-NP interaction in molecular details and elucidate its importance in influenza virus RNA synthesis and virus replication cycle. Influenza virus genomic RNA segments remain enwrapped with multiple copies of nucleoproteins (NP) in their oligomeric form and associate with viral RNA dependent RNA polymerase (RdRp), which perform viral gene expression at early stages of infection and genome replication at later stages. NS1 protein is a key virulence factor that counteracts host antiviral defense through modulating the activity of various host factors, indirectly creating a favorable environment for RNPs to perform viral RNA synthesis. Preliminary experiments confirmed that NS1 preferentially interacts with oligomeric NP, and overexpression of NS1 boosts RNP activity and viral RNA synthesis in a dose-dependent manner.

Total Budget (INR):

51,83,786

Organizations involved