SARS-CoV and IFN: Too Little, Too Late

Eveline Kindler, Volker Thiel, Eveline Kindler, Volker Thiel

Abstract

Dysregulated type I interferon (IFN-I) expression can lead to severe pathology and disease. In this issue of Cell Host & Microbe, Channappanavar et al. (2016) use a SARS-coronavirus animal model to describe how rapid and robust virus replication with delayed IFN-I can lead to lung immunopathology, with fatal outcomes.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Development of Lethal Pneumonia by Dysregulated IFN-I and Exaggerated Inflammatory Responses in SARS-CoV-Infected Mice Robust early SARS-CoV replication in the lung and delayed IFN-I expression (left panel) initiate a cascade of IFN-I mediated immune dysregulation. The upcoming IFN-I and cytokine response leads to recruitment of inflammatory monocyte-macrophages (IMMs) that, stimulated by pDC-derived IFN-I, release inflammatory mediators (CCR2 ligands; middle panel). This results in increased IMM influx, exuberant inflammation, and severe lung immunopathology. T cell responses are reduced through IFN-I-mediated T cell apoptosis (right panel). Possible preventive or therapeutic treatment options are early IFN-I treatment (left panel), inhibition of IFN-I signaling, IMM depletion, or cytokine neutralization (middle panel).

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Source: PubMed

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