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Baculovirus utilizes cholesterol transporter Niemann-Pick C1 for host cell entry

By Zhihong Li, Junhong Wei, Youpeng Fan, Xionge Mei, Qiang He, Yonghua Zhang, Tian Li, Mengxian Long, Jie Chen, TongBao Liu, Jialing Bao, Zhonghuai Xiang, Guoqing Pan, Chunfeng Li, Zeyang Zhou

Posted 02 May 2018
bioRxiv DOI: 10.1101/312744 (published DOI: 10.3389/fmicb.2019.02825)

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.

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