Baculovirus utilizes cholesterol transporter Niemann–Pick C1 for host cell entry
Baculovirus utilizes cholesterol transporter Niemann–Pick C1 for host cell entry
ABSTRACT The dual roles of baculovirus for the control of natural insect populations as an insecticide, and for foreign gene expression and delivery, have called for a comprehensive understanding of the molecular mechanisms governing viral infection. Here, we demonstrate that the Bombyx mori Niemann-Pick C1 (BmNPC1) is essential for baculovirus infection in insect cells. Both pretreatment of Bombyx mori embryonic cells (BmE) with NPC1 antagonists (imipramine or U18666A) and down-regulation of NPC1 expression resulted in a significant reduction in baculovirus BmNPV (Bombyx mori nuclear polyhedrosis virus) infectivity. Furthermore, we show that the major glycoprotein gp64 of BmNPV, responsible for both receptor binding and fusion, is able to interact predominantly with the BmNPC1 C domain, with an enhanced binding capacity at low pH conditions, indicating that NPC1 most likely plays a role during viral fusion in endosomal compartments. Our results, combined with previous studies identifying an essential role of hNPC1 in filovirus infection, suggest that the glycoprotein of several enveloped viruses possess a shared strategy of exploiting host NPC1 proteins during virus intracellular entry events. IMPORTANCEBmNPV is one of the most important members of the Baculoviridae; many viruses in this family have been frequently employed as viral vectors for foreign gene delivery or expression and as biopesticides, but their host receptors still remain unclear. Here, we describe that the intracellular cholesterol transporter BmNPC1 is indispensable for BmNPV infection in insect cells, and it interacts with the major viral glycoprotein gp64. Our study on the role of BmNPC1 in baculovirus infection has further expanded the list of the enveloped viruses that require host NPC1 proteins for entry, and will ultimately help us to uncover the molecular mechanism of the involvement of NPC1 proteins in the entry process of many enveloped viruses.
Liu TongBao、Fan Youpeng、Mei Xionge、Zhang Yonghua、Li Tian、Chen Jie、Xiang Zhonghuai、Bao Jialing、Long Mengxian、Zhou Zeyang、Li Zhihong、Wei Junhong、He Qiang、Li Chunfeng、Pan Guoqing
State Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest University||College of Life Sciences, Chongqing Normal UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest UniversityState Key Laboratory of Silkworm Genome Biology, Southwest University||Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest University
分子生物学昆虫学微生物学
BaculovirusNPC1host factorvirus entrycholesterol trafficking pathwayenveloped virusEbola virus
Liu TongBao,Fan Youpeng,Mei Xionge,Zhang Yonghua,Li Tian,Chen Jie,Xiang Zhonghuai,Bao Jialing,Long Mengxian,Zhou Zeyang,Li Zhihong,Wei Junhong,He Qiang,Li Chunfeng,Pan Guoqing.Baculovirus utilizes cholesterol transporter Niemann–Pick C1 for host cell entry[EB/OL].(2025-03-28)[2025-06-19].https://www.biorxiv.org/content/10.1101/312744.点此复制
评论