A Crisp(r) New Perspective on SARS-CoV-2 Biology

Abstract

Complementary genome-wide CRISPR-Cas9 screens performed by multiple groups reveal new insights into SARS-CoV-2 biology including aspects of viral entry, translation, replication, egress, and the genes regulating these processes. Comparisons with other coronaviruses enhances our understanding of the cellular life cycle of this medically important family of emerging viruses.

Figure 1

Proviral Host Factors Identified in Survival-Based CRISPR-Cas9 Screens Proviral proteins (or multi-factor complexes) (red) are shown adjacent to their putative sub-cellular localization (black) and presumptive role in the viral life cycle (purple). Following engagement of the cell surface receptor, SARS-CoV-2 enters cells via two possible mechanisms: endocytosis or fusion of the virion membrane with the plasma membrane. In the cytoplasm, the RNA genome undergoes translation and replication, and sub-genomic RNA transcripts are generated. Structural gene translation occurs in the rough endoplasmic reticulum (ER), with virion assembly, maturation, and post-transcriptional modification occurring across the ER, ER-Golgi intermediate compartment (ERGIC), and Golgi network through a poorly understood process. Virions traffic to the cell surface via lysosomes and/or other vesicles capable of exocytosis. Endosomal recycling and interactions between the endosome and lysosome are thought to play roles in viral egress but are currently poorly defined.