To prevent signaling downstream of IFN release, CoV proteins inhibit several steps of the signal transduction pathway that bridge the receptor subunits (IFNAR1 and IFNAR2) to the STAT proteins that activate transcription. For SARS-CoV-1, these mechanisms include IFNAR1 degradation by ORF3a (Minakshi et al., 2009), decreased STAT1 phosphorylation by NSP1 (Wathelet et al., 2007), and antagonism of STAT1 nuclear translocation by ORF6 (Frieman et al., 2007, Kopecky-Bromberg et al., 2007). However, SARS-CoV-2 ORF6 shares only 69% sequence homology with SARS-CoV-1, suggesting this function may not be conserved. In support of this notion, SARS-CoV-2 infection fails to limit STAT1 phosphorylation, unlike in SARS-CoV-1 infection (Lokugamage et al., 2020).