Interferons (IFNs) inhibit severe acute respiratory syndrome coronavirus (SARS-CoV) replication and might be valuable for SARS treatment. In this study, we demonstrate that treatment of Vero E6 cells with interleukin-4 (IL-4) decreased the susceptibility of these cells to SARS-CoV infection. In contrast to IFNs, IL-4 did not show antiviral activity when administered immediately after SARS-CoV infection, suggesting that IL-4 acts early during the SARS-CoV replication cycle. Indeed, binding of recombinant SARS-CoV spike protein to Vero E6 cells was diminished on cells treated with IL-4, but also on cells exposed to IFN-γ. Consistent with these observations, IL-4 and IFN-γ downregulated cell surface expression of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Besides diminished ACE2 cell surface expression, ACE2 mRNA levels were also decreased after treatment with these cytokines. These findings suggest that IL-4 and IFN-γ inhibit SARS-CoV replication partly through downregulation of ACE2.

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Department of Virology

de Lang, A., Osterhaus, A., & Haagmans, B. (2006). Interferon-γ and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells. Virology, 353(2), 474–481. doi:10.1016/j.virol.2006.06.011