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
![](https://static.wixstatic.com/media/84558f_cf3c6bdee1f64e038b6d01120a9e3563~mv2.png/v1/fill/w_49,h_35,al_c,q_85,usm_0.66_1.00_0.01,blur_2,enc_auto/84558f_cf3c6bdee1f64e038b6d01120a9e3563~mv2.png)