Consistent with a direct relationship between TFEB activation, IFITM2/3 turnover, and Spike-mediated cell entry, we found that ectopic expression of a constitutively active form of TFEB lacking the first 30 amino-terminal residues [50] was sufficient to trigger IFITM2/3 loss from cells (Figure 6E) and sufficient to increase susceptibility to HIV-CoV-2 infection (Figure 6F). Here, TFEB is linked to COVID-19.