Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus

Martin Spiegel,Friedemann Weber

doi:10.1186/1743-422x-3-17

Abstract

BackgroundSARS coronavirus (SARS-CoV) is the etiologic agent of the severe acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. Here, we investigated the cytokine response of two human non-lymphatic cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV.ResultsA comparison with established cytokine-inducing viruses revealed that SARS-CoV only weakly triggered a cytokine response. In particular, SARS-CoV did not activate significant transcription of the interferons IFN-α, IFN-β, IFN-λ1, IFN-λ2/3, as well as of the interferon-induced antiviral genes ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly, however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293.ConclusionOur data indicate that SARS-CoV suppresses the antiviral cytokine system of non-immune cells to a large extent, thus buying time for dissemination in the host. However, synthesis of IP-10 and IL-8, which are established markers for acute-stage SARS, escapes the virus-induced silencing at least in some cell types. Therefore, the progressive infiltration of immune cells into the infected lungs observed in SARS patients could be due to the production of these chemokines by the infected tissue cells.

Highlights

SARS coronavirus (SARS-CoV) is the etiologic agent of the severe acute respiratory syndrome
Our data indicate that SARS-CoV suppresses the antiviral cytokine system of nonimmune cells to a large extent, buying time for dissemination in the host
The progressive infiltration of immune cells into the infected lungs observed in SARS patients could be due to the production of these chemokines by the infected tissue cells

Summary

Introduction

SARS coronavirus (SARS-CoV) is the etiologic agent of the severe acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. The initial encounter with the host takes place in cells of non-lymphatic origin. The outcome of this primary infection can determine the course of disease, and the cytokine response of the infected cell plays a vital part. Type I interferons (IFN-α/β) are potent, antivirally active cytokines which can be produced by most, if not all, body cells in response to virus infection. On the other hand, have evolved various mechanisms to counteract the host's cytokine response [3], and their ability to induce or inhibit cytokine production in infected cells has direct consequences for the balance between host defense and virus propagation

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