Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, 332-0012, Japan.
Commun Biol. 2022 Jul 19;5(1):694. doi: 10.1038/s42003-022-03581-9.
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. However, our understanding of the interaction between HSV-1 and human host factors remains incomplete. Here, to identify the host factors for HSV-1 infection, 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 host factor for HSV-1 infection. 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 further insights into the host factor requirements for HSV-1 infection and HepS biosynthesis.
单纯疱疹病毒 1 型（HSV-1）是一种普遍存在的病原体，可导致人类发生各种疾病，从常见的粘膜皮肤损伤到严重的危及生命的脑炎。然而，我们对 HSV-1 与人类宿主因素之间相互作用的理解仍不完整。在这里，为了鉴定 HSV-1 感染的宿主因素，我们使用近单倍体 HAP1 细胞进行了人类全基因组 CRISPR 筛选，在该细胞中可以有效地实现基因敲除（KO）。除了几个已经确定的宿主因素外，我们还鉴定出 3'-磷酸腺苷 5'-磷酸硫酸合酶 1（PAPSS1）是 HSV-1 感染的宿主因素。HAP1 细胞中 PAPSS1 的 KO 降低了肝素硫酸酯（HepS）的表达，从而减少了 HSV-1 和其他几种 HepS 依赖性病毒（如 HSV-2、乙型肝炎病毒和一种人类季节性冠状病毒）的结合。因此，我们的发现进一步深入了解了 HSV-1 感染和 HepS 生物合成的宿主因素要求。
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