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Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection

In this new publication in Nature Immunology, Qiwen Teo (co-first author), HKU-Pasteur PhD student who just graduated, Chris Mok and Sumana Sanyal, both former PIs at HKU-Pasteur, tried to address the scientific question of the function of ISG15 (a downstream antiviral protein of IFN) regulation during the infection of SARS-CoV-2, influenza or Zika viruses.

They found that while influenza and Zika viruses induce ISGylation, SARS-CoV-2 triggers deISGylation instead to generate free ISG15. The altered free and conjugated ISG15 dysregulates macrophage responses and probably contributes to the cytokine storms triggered by SARS-CoV-2. Their findings thus provide a new angle to understand the pathogenesis of the SARS-CoV-2. “The novel coronavirus SARS-CoV-2 has caused more than 240 million cases of COVID-19 and over 5 millions deaths. To face this challenge, interferons (IFNs) are the first line of defence against virus infections and are critical drivers of the innate immune response.Chris Mok

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