IFN-λ1 Displays Various Levels of Antiviral Activity In Vitro in a Select Panel of RNA Viruses.

Marina Plotnikova,Mariia Sergeeva,Konstantin Kаа,Sergey Klotchenko,Alexey Lozhkov,Andrey Vasin,Ekaterina Romanovskaya-Romanko,Irina Baranovskaya

doi:10.3390/v13081602

Abstract

Type III interferons (lambda IFNs) are a quite new, small family of three closely related cytokines with interferon-like activity. Attention to IFN-λ is mainly focused on direct antiviral activity in which, as with IFN-α, viral genome replication is inhibited without the participation of immune system cells. The heterodimeric receptor for lambda interferons is exposed mainly on epithelial cells, which limits its possible action on other cells, thus reducing the likelihood of developing undesirable side effects compared to type I IFN. In this study, we examined the antiviral potential of exogenous human IFN-λ1 in cellular models of viral infection. To study the protective effects of IFN-λ1, three administration schemes were used: ‘preventive’ (pretreatment); ‘preventive/therapeutic’ (pre/post); and ‘therapeutic’ (post). Three IFN-λ1 concentrations (from 10 to 500 ng/mL) were used. We have shown that human IFN-λ1 restricts SARS-CoV-2 replication in Vero cells with all three treatment schemes. In addition, we have shown a decrease in the viral loads of CHIKV and IVA with the ‘preventive’ and ‘preventive/therapeutic’ regimes. No significant antiviral effect of IFN-λ1 against AdV was detected. Our study highlights the potential for using IFN-λ as a broad-spectrum therapeutic agent against respiratory RNA viruses.

Highlights

Interferons (IFNs) play a critical role in the immune response, by suppressing the spread of viral infection in the early stages of illness, and they form the first line of defense in mammals against viral infection [1,2]
The action of IFN-λ is realized through the heterodimeric IFNLR receptor, which consists of the IFNλR1 and IL10R2 subunits
A549 cells (Supplementary, Figure S2), we showed a tendency towards an increase in the production of viral NP protein in response to IFN-λ1 treatment of cells immediately after infection

Summary

Introduction

Interferons (IFNs) play a critical role in the immune response, by suppressing the spread of viral infection in the early stages of illness, and they form the first line of defense in mammals against viral infection [1,2]. Type III IFN (IFN-λ) is a group of IFNs related to IFN-α/β, showing similar antiviral effects [3,4]. The action of IFN-λ is realized through the heterodimeric IFNLR receptor, which consists of the IFNλR1 and IL10R2 subunits. The IL10R2 subunit is part of receptor complexes for IL-10, IL-22, and IL-26; it is expressed in the cells of various tissues [6]. The IFNλR1 subunit exhibits limited cellular distribution. A high level of IFNλR1 has been noted in the lungs, intestines, liver, and upper epidermis [7]

Methods

Results

Discussion

Conclusion