Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection

Front Immunol. 2024 Jan 15:14:1273604. doi: 10.3389/fimmu.2023.1273604. eCollection 2023.

Abstract

Mammalians sense antigenic messages from infectious agents that penetrate the respiratory and digestive epithelium, as well as signals from damaged host cells through membrane and cytosolic receptors. The transduction of these signals triggers a personalized response, depending on the nature of the stimulus and the host's genetics, physiological condition, and comorbidities. Interferons (IFNs) are the primary effectors of the innate immune response, and their synthesis is activated in most cells within a few hours after pathogen invasion. IFNs are primarily synthesized in infected cells, but their anti-infective effect is extended to the neighboring cells by autocrine and paracrine action. The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 2019 was a stark reminder of the potential threat posed by newly emerging viruses. This pandemic has also triggered an overwhelming influx of research studies aiming to unveil the mechanisms of protective versus pathogenic host immune responses induced by SARS-CoV-2. The purpose of this review is to describe the role of IFNs as vital players in the battle against SARS-CoV-2 infection. We will briefly characterize and classify IFNs, present the inductors of IFN synthesis, their sensors, and signaling pathways, and then discuss the role of IFNs in controlling the evolution of SARS-CoV-2 infection and its clinical outcome. Finally, we will present the perspectives and controversies regarding the prophylactic and therapeutic potential of IFNs in SARS-CoV-2 infection.

Keywords: SARS-CoV-2; interferons; receptors; signal transduction pathways; therapeutic role of IFNs.

Publication types

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

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • COVID-19*
  • Immunity, Innate
  • Interferons* / metabolism
  • Mammals / metabolism
  • SARS-CoV-2 / metabolism

Substances

  • Interferons
  • Antiviral Agents

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Romanian Executive Agency for Higher Education, Research, Development, and Innovation (https://uefiscdi.gov.ro/, accessed on 20 April 2023) research project FDI 0690/2023, “The core program within the National Research Development and Innovation Plan, 2022–2027”, carried out with the support of the Ministry of Research, Innovation and Digitalization (MCID), project no. 23020101, Contract no. 7N from 3 January 2023, and the “Analysis of the potential for sustainable use of vegetation specific to the Danube-Danube Delta-Black Sea system” project, awarded by the European Regional Development Fund through the Competitiveness Operational Program 2014–2020, contract no. 108630.The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.