Baculovirus Utilizes Cholesterol Transporter NIEMANN–Pick C1 for Host Cell Entry
The dual roles of baculovirus for the control of natural insect populations as an insecticide, and as a tool 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 Nieman...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.02825/full |
| _version_ | 1819131079236255744 |
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| author | Zhihong Li Zhihong Li Youpeng Fan Youpeng Fan Junhong Wei Junhong Wei Junhong Wei Xionge Mei Qiang He Qiang He Yonghua Zhang Tian Li Tian Li Tian Li Mengxian Long Mengxian Long Mengxian Long Jie Chen Jie Chen Jie Chen Jialing Bao Jialing Bao Jialing Bao Guoqing Pan Guoqing Pan Guoqing Pan Chunfeng Li Chunfeng Li Chunfeng Li Zeyang Zhou Zeyang Zhou Zeyang Zhou Zeyang Zhou |
| author_facet | Zhihong Li Zhihong Li Youpeng Fan Youpeng Fan Junhong Wei Junhong Wei Junhong Wei Xionge Mei Qiang He Qiang He Yonghua Zhang Tian Li Tian Li Tian Li Mengxian Long Mengxian Long Mengxian Long Jie Chen Jie Chen Jie Chen Jialing Bao Jialing Bao Jialing Bao Guoqing Pan Guoqing Pan Guoqing Pan Chunfeng Li Chunfeng Li Chunfeng Li Zeyang Zhou Zeyang Zhou Zeyang Zhou Zeyang Zhou |
| author_sort | Zhihong Li |
| collection | DOAJ |
| description | The dual roles of baculovirus for the control of natural insect populations as an insecticide, and as a tool 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 B. mori embryonic cells (BmE) with NPC1 antagonists (imipramine or U18666A) and down-regulation of NPC1 expression resulted in a significant reduction in baculovirus BmNPV (B. mori nuclear polyhedrosis virus) infectivity. Disruption of BmNPC1 could decrease viral entry (2 hpi) rather than reduce the viral binding to the BmE cells. Furthermore, our results showed that NPC1 domain C binds directly and specifically to the viral glycoprotein GP64, which is responsible for both receptor binding and fusion. Antibody blocking assay also revealed that the domain C specific polyclonal antibody inhibited BmNPV infection, indicating that NPC1 domain C most likely plays a role during viral fusion in endosomal compartments. Our results, combined with previous studies identifying an essential role of human NPC1 (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. |
| first_indexed | 2024-12-22T09:09:48Z |
| format | Article |
| id | doaj.art-7c63f650b0ec4345833c8065a3b4becb |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T09:09:48Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-7c63f650b0ec4345833c8065a3b4becb2022-12-21T18:31:27ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-12-011010.3389/fmicb.2019.02825496888Baculovirus Utilizes Cholesterol Transporter NIEMANN–Pick C1 for Host Cell EntryZhihong Li0Zhihong Li1Youpeng Fan2Youpeng Fan3Junhong Wei4Junhong Wei5Junhong Wei6Xionge Mei7Qiang He8Qiang He9Yonghua Zhang10Tian Li11Tian Li12Tian Li13Mengxian Long14Mengxian Long15Mengxian Long16Jie Chen17Jie Chen18Jie Chen19Jialing Bao20Jialing Bao21Jialing Bao22Guoqing Pan23Guoqing Pan24Guoqing Pan25Chunfeng Li26Chunfeng Li27Chunfeng Li28Zeyang Zhou29Zeyang Zhou30Zeyang Zhou31Zeyang Zhou32State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaDepartment of Microbiology, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaChongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaChongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, ChinaKey Laboratory for Sericulture Functional Genomics Biotechnology of Agricultural Ministry, Southwest University, Chongqing, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaChongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaChongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, ChinaKey Laboratory for Sericulture Functional Genomics Biotechnology of Agricultural Ministry, Southwest University, Chongqing, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaChongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, ChinaKey Laboratory for Sericulture Functional Genomics Biotechnology of Agricultural Ministry, Southwest University, Chongqing, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaChongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, ChinaKey Laboratory for Sericulture Functional Genomics Biotechnology of Agricultural Ministry, Southwest University, Chongqing, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaChongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, ChinaKey Laboratory for Sericulture Functional Genomics Biotechnology of Agricultural Ministry, Southwest University, Chongqing, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaChongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, ChinaKey Laboratory for Sericulture Functional Genomics Biotechnology of Agricultural Ministry, Southwest University, Chongqing, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaChongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, ChinaKey Laboratory for Sericulture Functional Genomics Biotechnology of Agricultural Ministry, Southwest University, Chongqing, ChinaState Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, ChinaChongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, ChinaKey Laboratory for Sericulture Functional Genomics Biotechnology of Agricultural Ministry, Southwest University, Chongqing, ChinaCollege of Life Sciences, Chongqing Normal University, Chongqing, ChinaThe dual roles of baculovirus for the control of natural insect populations as an insecticide, and as a tool 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 B. mori embryonic cells (BmE) with NPC1 antagonists (imipramine or U18666A) and down-regulation of NPC1 expression resulted in a significant reduction in baculovirus BmNPV (B. mori nuclear polyhedrosis virus) infectivity. Disruption of BmNPC1 could decrease viral entry (2 hpi) rather than reduce the viral binding to the BmE cells. Furthermore, our results showed that NPC1 domain C binds directly and specifically to the viral glycoprotein GP64, which is responsible for both receptor binding and fusion. Antibody blocking assay also revealed that the domain C specific polyclonal antibody inhibited BmNPV infection, indicating that NPC1 domain C most likely plays a role during viral fusion in endosomal compartments. Our results, combined with previous studies identifying an essential role of human NPC1 (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.https://www.frontiersin.org/article/10.3389/fmicb.2019.02825/fullBombyx moriBmNPVNPC1cholesterol trafficking pathwayenveloped virus |
| spellingShingle | Zhihong Li Zhihong Li Youpeng Fan Youpeng Fan Junhong Wei Junhong Wei Junhong Wei Xionge Mei Qiang He Qiang He Yonghua Zhang Tian Li Tian Li Tian Li Mengxian Long Mengxian Long Mengxian Long Jie Chen Jie Chen Jie Chen Jialing Bao Jialing Bao Jialing Bao Guoqing Pan Guoqing Pan Guoqing Pan Chunfeng Li Chunfeng Li Chunfeng Li Zeyang Zhou Zeyang Zhou Zeyang Zhou Zeyang Zhou Baculovirus Utilizes Cholesterol Transporter NIEMANN–Pick C1 for Host Cell Entry Frontiers in Microbiology Bombyx mori BmNPV NPC1 cholesterol trafficking pathway enveloped virus |
| title | Baculovirus Utilizes Cholesterol Transporter NIEMANN–Pick C1 for Host Cell Entry |
| title_full | Baculovirus Utilizes Cholesterol Transporter NIEMANN–Pick C1 for Host Cell Entry |
| title_fullStr | Baculovirus Utilizes Cholesterol Transporter NIEMANN–Pick C1 for Host Cell Entry |
| title_full_unstemmed | Baculovirus Utilizes Cholesterol Transporter NIEMANN–Pick C1 for Host Cell Entry |
| title_short | Baculovirus Utilizes Cholesterol Transporter NIEMANN–Pick C1 for Host Cell Entry |
| title_sort | baculovirus utilizes cholesterol transporter niemann pick c1 for host cell entry |
| topic | Bombyx mori BmNPV NPC1 cholesterol trafficking pathway enveloped virus |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.02825/full |
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