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

Nat Genet. 2021 Apr;53(4):435-444. doi: 10.1038/s41588-021-00805-2. Epub 2021 Mar 8.


The ongoing COVID-19 pandemic has caused a global economic and health crisis. To identify host factors essential for coronavirus infection, we performed genome-wide functional genetic screens with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus 229E. These screens uncovered virus-specific as well as shared host factors, including TMEM41B and PI3K type 3. We discovered that SARS-CoV-2 requires the lysosomal protein TMEM106B to infect human cell lines and primary lung cells. TMEM106B overexpression enhanced SARS-CoV-2 infection as well as pseudovirus infection, suggesting a role in viral entry. Furthermore, single-cell RNA-sequencing of airway cells from patients with COVID-19 demonstrated that TMEM106B expression correlates with SARS-CoV-2 infection. The present study uncovered a collection of coronavirus host factors that may be exploited to develop drugs against SARS-CoV-2 infection or future zoonotic coronavirus outbreaks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchoalveolar Lavage Fluid / cytology
  • COVID-19 / epidemiology
  • COVID-19 / genetics*
  • COVID-19 / virology
  • CRISPR-Cas Systems*
  • Cell Line, Tumor
  • Cells, Cultured
  • Coronavirus 229E, Human / genetics
  • Epidemics
  • Epithelial Cells / virology
  • Gene Expression
  • Genome, Human / genetics*
  • Genome-Wide Association Study / methods*
  • Host-Pathogen Interactions
  • Humans
  • Membrane Proteins / genetics*
  • Nerve Tissue Proteins / genetics*
  • Proviruses / physiology
  • SARS-CoV-2 / physiology
  • Virus Internalization


  • Membrane Proteins
  • Nerve Tissue Proteins
  • TMEM106B protein, human