Genome-wide CRISPR screening identifies TMEM106B as a proviral host factor for SARS-CoV-2

By using a CRISPR knock-out library applied for Huh7 hepatocellular carcinoma cell line, a host factor TMEM106B was identified to support the SARS-CoV-2 infection. TMEM106B resides in endosomes and lysosomes, and controls lysosome size, number, mobility and trafficking. TMEM106B is involved in the endosomal acidification that may facilitate delivery of SARS-CoV-2 genome into the cytoplasm. Alternatively, TMEM106B may be an endosomal receptor for SARS-CoV-2; this relationship resembles the interaction between Ebola virus and its lysosomal receptor NPC1. In human airway epithelia, cells with higher TMEM106B expression were susceptible for SARS-COV-2 infection, which was demonstrated by single cell RNA-seq dataset from COVID-19 patients. It was also speculated from these data that SARS-CoV-2 infection induces the expression of TMEM106B. The expression of TMEM106B is higher in the brain and testis. Several evidences show that SARS-CoV-2 infection causes neurological symptoms such as stroke, brain hemorrhage, and memory loss. Moreover, a study demonstrated that impaired sperm quality was observed in patients with COVID-19. These extra-respiratory pathogenesis of SARS-CoV-2 infection may be explained by the correlation of TMEM106B expression with viral infection.