EFFECT OF LONG NONCODING RNA NEAT1 ON RIG-I-MEDIATED SIGNALING PATHWAY IN INFLUENZA A VIRAL INFECTION



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Abstract

Acute respiratory viral infections, including influenza A, pose a global medical, social, and economic challenge. The high variability and contagiousness of the influenza A virus necessitate an in-depth study of the molecular mechanisms for interaction between the pathogen and the host immune system to develop new efficient strategies. Noncoding RNAs – regulatory molecules that influence numerous cellular processes, including the immune response, – are of great interest in this context. Objective: To study an effect of long noncoding RNA NEAT1 on influenza A (H1N1) virus replication and the expression of key components of the innate immune response associated with RIG-I-like receptor signaling pathways. Methods: The study utilized the human lung carcinoma cell line A549. The cells were infected with influenza A virus strain A/WSN/1933 (H1N1). NEAT1 expression was inhibited using specific antisense oligonucleotides. Real-time PCR was used to assess the expression levels for NEAT1, viral RNA, genes of RLR family receptors (RIG-I, MDA5, LGP2) and immune response effector molecules (NF-κB, IL-1β, IFN-α, IFN-β) at 24 and 48 hours post-infection. Results: Infection with influenza A virus resulted in significantly increased NEAT1 expression. NEAT1 inhibition was accompanied by a 9.19- and 3.03-fold increase in intracellular viral RNA replication after 24 and 48 hours, respectively. At 24 hours post-infection, NEAT1 inhibition increased the expression of the RIG-I receptor gene as well as IFN-α and IFN-β interferon genes. At 48 hours, the opposite trend was observed: upon NEAT1 inhibition, the expression levels of IFN-α and IFN-β genes, as well as NF-κB p65 subunit were significantly reduced. Conclusions: Long non-coding RNA NEAT1 plays an important role in the antiviral response to influenza A, exerting a suppressive effect on H1N1 virus replication. The influence of NEAT1 on the expression of RLR signaling pathway components is complex and dynamic: early in infection (24 hours), NEAT1 can exert a suppressive effect on immune response factors, whereas later (48 hours), it acts as a positive regulator for the expression of key effector molecules (IFN-α, IFN-β, NF-κB). These findings expand our understanding on innate immunity mechanisms and indicate the potential for NEAT1 as a target for therapeutic and diagnostic strategies.

About the authors

Ekaterina A. Meremianina

I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russian Federation;
FSBEI FPE "Russian Medical Academy of Continuous Professional Education" MOH, Moscow, Russian Federation

Email: ekaterina@meremianina.ru
ORCID iD: 0000-0003-4334-1473
SPIN-code: 9721-4839

PhD (Medicine), Senior Researcher, Associate Professor, Department of Virology 

Russian Federation, 105064, Russian Federation, Moscow, Maly Kazenny Lane, 5a; 125993, Russian Federation, Moscow, Barrikadnaya St., 2/1, building 1

Yulia I. Ammour

I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russian Federation

Email: yulia.ammour@yahoo.fr

PhD (Biology), Head of the Laboratory of Oncolytic Viruses

Russian Federation, 105064, Russian Federation, Moscow, Maly Kazenny Lane, 5a

Natalya D. Abramova

I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russian Federation

Email: and960911@gmail.com
ORCID iD: 0000-0002-7307-0515
SPIN-code: 1763-8942

PhD (Medicine), Researcher, Laboratory of Oncolytic Viruses and Laboratory of Molecular Immunology

Russian Federation, 105064, Moscow, Maly Kazenny Lane, 5a

Oxana A. Svitich

I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russian Federation;
I.M. Sechenov State Medical University, Moscow, Russian Federation

Email: svitichoa@yandex.ru
ORCID iD: 0000-0003-1757-8389

RAS Full Member, DSc (Medicine), Director, Professor

Russian Federation, 105064, Russian Federation, Moscow, Maly Kazenny Lane, 5a; 119435, Moscow, Bolshaya Pirogovskaya St., 2, building 2

Natalia O. Kalyuzhnaya

I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russian Federation

Author for correspondence.
Email: nat_kalyuzhnaya@mail.ru
ORCID iD: 0000-0002-1668-1846
SPIN-code: 7169-6807
Scopus Author ID: 58648143400

Junior Researcher, Laboratory of Oncolytic Viruses and Laboratory of Molecular Immunology

Russian Federation, 105064, Russian Federation, Moscow, Maly Kazenny Lane, 5a

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