key: cord-0724657-k44142tr
authors: Jouvenet, Nolwenn; Goujon, Caroline; Banerjee, Arinjay
title: Clash of the titans: interferons and SARS-CoV-2
date: 2021-10-16
journal: Trends Immunol
DOI: 10.1016/j.it.2021.10.009
sha: 62823f21ae133879825ac9a22fc63af5d52c3f11
doc_id: 724657
cord_uid: k44142tr

Interferons are our first line of defense against invading viruses. However, viruses encode effector proteins that can modulate human interferon responses. In this forum article, we highlight important discoveries and discuss outstanding questions that will enable us to better understand the nuances of this evolutionary battle between interferons and SARS-CoV-2.

proposed [4] , but this remains controversial. Depleting the expression of the laboratory of 51 genetics and physiology 2 (LGP2) gene --a known potentiator of MDA5-mediated IFN 52 responses --significantly reduced type I IFN (IFN) mRNA abundance in SARS-CoV-2 53 infected Calu-3 cells [2] . Collectively, these results highlight the concept that MDA5 is 54 particularly important for inducing type I and III IFN responses against SARS-CoV-2. PRRs 55 other than MDA5 are likely to contribute to the initiation of host cell responses against SARS-56

CoV-2 infection but remain largely unidentified. Of note, interleukin 6 (IL6) induction seems 57 to depend on RIG-I and not MDA5 expression in SARS-CoV-2 infected Calu-3 cells that 58 were depleted for these RLRs using RNA interference (RNAi) [4] . RLR usage may thus 59 trigger the expression of different inflammatory mediators and vary depending on cell type. 

Dynamic innate immune response determines 181 susceptibility to SARS-CoV-2 infection and early replication kinetics

Impaired type I interferon activity and inflammatory 184 responses in severe COVID-19 patients

Susceptibility to severe COVID-19

Type I Interferon Susceptibility Distinguishes SARS-188

CoV-2 from SARS-CoV

Functional landscape of SARS-CoV-2 cellular 190 restriction

LY6E impairs coronavirus fusion and confers immune 192 control of viral disease