2. Academic Validation
  3. EXTL3 and NPC1 are mammalian host factors for Autographa californica multiple nucleopolyhedrovirus infection

EXTL3 and NPC1 are mammalian host factors for Autographa californica multiple nucleopolyhedrovirus infection

  • Nat Commun. 2024 Sep 4;15(1):7711. doi: 10.1038/s41467-024-52193-w.
Yuege Huang # 1,  Hong Mei # 2,  Chunchen Deng 3 4,  Wei Wang 3,  Chao Yuan 3 4,  Yan Nie 3,  Jia-Da Li 5 6,  Jia Liu 7 8 9 10 11
Affiliations

Affiliations

  • 1 Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
  • 2 Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China. meihong@shanghaitech.edu.cn.
  • 3 Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.
  • 4 School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • 5 Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China. lijiada@sklmg.edu.cn.
  • 6 Hunan Key Laboratory of Animal Models for Human Diseases, Changsha, Hunan, China. lijiada@sklmg.edu.cn.
  • 7 Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China. liujia@shanghaitech.edu.cn.
  • 8 School of Life Science and Technology, ShanghaiTech University, Shanghai, China. liujia@shanghaitech.edu.cn.
  • 9 Shanghai Clinical Research and Trial Center, Shanghai, China. liujia@shanghaitech.edu.cn.
  • 10 Guangzhou Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong, China. liujia@shanghaitech.edu.cn.
  • 11 Shanghai Asiflyerbio Biotechnology, Shanghai, China. liujia@shanghaitech.edu.cn.
  • # Contributed equally.
PMID: 39231976 DOI: 10.1038/s41467-024-52193-w
Abstract

Baculovirus is an obligate parasitic virus of the phylum Arthropoda. Baculovirus including Autographa californica multiple nucleopolyhedrovirus (AcMNPV) has been widely used in the laboratory and industrial preparation of proteins or protein complexes. Due to its large packaging capacity and non-replicative and non-integrative natures in mammals, baculovirus has been proposed as a gene therapy vector for transgene delivery. However, the mechanism of baculovirus transduction in mammalian cells has not been fully illustrated. Here, we employed a cell surface protein-focused CRISPR screen to identify host dependency factors for baculovirus transduction in mammalian cells. The screening experiment uncovered a series of baculovirus host factors in human cells, including exostosin-like Glycosyltransferase 3 (EXTL3) and NPC intracellular Cholesterol transporter 1 (NPC1). Further investigation illustrated that EXTL3 affected baculovirus attachment and entry by participating in heparan sulfate biosynthesis. In addition, NPC1 promoted baculovirus transduction by mediating membrane fusion and endosomal escape. Moreover, in vivo, baculovirus transduction in Npc1-/+ mice showed that disruption of Npc1 gene significantly reduced baculovirus transduction in mouse liver. In summary, our study revealed the functions of EXTL3 and NPC1 in baculovirus attachment, entry, and endosomal escape in mammalian cells, which is useful for understanding baculovirus transduction in human cells.

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