A genome-wide CRISPR screen for herpes simplex virus type-1 host factors reveals PAPS synthase as a key factor for heparan sulfate biosynthesis. Homo sapiens

Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen that causes various diseases in humans, ranging from common mucocutaneous lesions to severe life-threatening encephalitis. Therefore, to identify the host factors for HSV-1 infections, we performed a human genome-wide CRISPR screen using near-haploid HAP1 cells, in which gene knockout (KO) could be efficiently achieved. Along with several already known host factors, we identified 3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) as a novel factor for HSV-1 infections. The KO of PAPSS1 in HAP1 cells reduced heparan sulfate (HepS) expression, consequently diminishing the binding of HSV-1 and several other HepS-dependent viruses (such as HSV-2, hepatitis B virus, and a human seasonal coronavirus). Hence, our findings provide new insights into the host factor requirements for HSV-1 infection and HepS biosynthesis.