Apoptosis or Antiapoptosis? Interrupted Regulated Cell Death of Host Cells by Ascovirus Infection In Vitro
ABSTRACT Ascoviruses are insect-specific viruses thought to utilize the cellular apoptotic processes of host larvae to produce numerous virion-containing vesicles. In this study, we first determined the biochemical characteristics of ascovirus-infected, in vitro-cultured insect cells and the possibl...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-02-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03119-22 |
| _version_ | 1811163383524753408 |
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| author | Huan Yu Jin-Rong Li Hua-Yan Xiao Sheng-Kai Cao Bin Chen Ni Li Gong Chen Guo-Hua Huang |
| author_facet | Huan Yu Jin-Rong Li Hua-Yan Xiao Sheng-Kai Cao Bin Chen Ni Li Gong Chen Guo-Hua Huang |
| author_sort | Huan Yu |
| collection | DOAJ |
| description | ABSTRACT Ascoviruses are insect-specific viruses thought to utilize the cellular apoptotic processes of host larvae to produce numerous virion-containing vesicles. In this study, we first determined the biochemical characteristics of ascovirus-infected, in vitro-cultured insect cells and the possible antiapoptotic capacity of ascovirus-infected insect cells. The results indicated that the ascovirus infection in the first 24 h was different from the infection from 48 h to the later infection stages. In the early infection stage, the Spodoptera exigua host cells had high membrane permeability and cleaved gasdermin D (GSDMD) but uncleaved Casp-6 (SeCasp-6). In contrast, the later infection stage had no such increased membrane permeability and had cleaved SeCasp-6. Four different chemicals were used to induce apoptosis at different stages of ascovirus infection: hydrogen peroxide (H2O2) and actinomycin D (ActD) had similar effects on the ascovirus-infected cells, whereas cMYC inhibitors and tumor necrosis factor alpha (TNF-α) plus SM-164 apoptosis inducers (T/S) had similar effects on infected cells. The former two inducers inhibited viral DNA replication in most situations, while the latter two inducers inhibited viral DNA replication in the early stage of infection but promoted viral DNA replication in the later infection stage. Furthermore, immunoblotting assays verified that T/S treatment could increase the expression levels of viral major capsid protein (MCP) and the host inhibitor of apoptosis protein (SeIAP). Coimmunoprecipitation assays revealed interaction between SeIAP and SeCasps, but this interaction was disturbed in ascovirus-infected cells. This study details the in vitro infection process of ascovirus, indicating the utilization of pyroptosis for antiapoptosis cytopathology. IMPORTANCE Clarifying the relationship between different types of viral infections and host regulation of cell death (RCD) can provide insights into the interaction between viruses and host cells. Ascoviruses are insect-specific viruses with apoptosis-utilizing-like infection cytopathology. However, RCD does not only include apoptosis, and while in our previous transmission electron microscopic observations, ascovirus-infected cells did not show typical apoptotic characteristics (unpublished data), in this study, they did show increased membrane permeability. These results indicate that the cytopathology of ascovirus infection is a complex process in which the virus manipulates host RCD. The RCD of insect cells is quite different from that of mammals, and studies on the former are many fewer than those on the latter, especially in the case of RCD in lepidopteran insects. Our results will lay a foundation for understanding the RCD of lepidopteran insects and its function in the process of insect virus infection. |
| first_indexed | 2024-04-10T06:44:13Z |
| format | Article |
| id | doaj.art-99fa557a39034125a9e5d0ad686a6c15 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-10T06:44:13Z |
| publishDate | 2023-02-01 |
| publisher | American Society for Microbiology |
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| spelling | doaj.art-99fa557a39034125a9e5d0ad686a6c152023-02-28T14:06:24ZengAmerican Society for MicrobiologymBio2150-75112023-02-0114110.1128/mbio.03119-22Apoptosis or Antiapoptosis? Interrupted Regulated Cell Death of Host Cells by Ascovirus Infection In VitroHuan Yu0Jin-Rong Li1Hua-Yan Xiao2Sheng-Kai Cao3Bin Chen4Ni Li5Gong Chen6Guo-Hua Huang7Hunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Changsha, Hunan, ChinaABSTRACT Ascoviruses are insect-specific viruses thought to utilize the cellular apoptotic processes of host larvae to produce numerous virion-containing vesicles. In this study, we first determined the biochemical characteristics of ascovirus-infected, in vitro-cultured insect cells and the possible antiapoptotic capacity of ascovirus-infected insect cells. The results indicated that the ascovirus infection in the first 24 h was different from the infection from 48 h to the later infection stages. In the early infection stage, the Spodoptera exigua host cells had high membrane permeability and cleaved gasdermin D (GSDMD) but uncleaved Casp-6 (SeCasp-6). In contrast, the later infection stage had no such increased membrane permeability and had cleaved SeCasp-6. Four different chemicals were used to induce apoptosis at different stages of ascovirus infection: hydrogen peroxide (H2O2) and actinomycin D (ActD) had similar effects on the ascovirus-infected cells, whereas cMYC inhibitors and tumor necrosis factor alpha (TNF-α) plus SM-164 apoptosis inducers (T/S) had similar effects on infected cells. The former two inducers inhibited viral DNA replication in most situations, while the latter two inducers inhibited viral DNA replication in the early stage of infection but promoted viral DNA replication in the later infection stage. Furthermore, immunoblotting assays verified that T/S treatment could increase the expression levels of viral major capsid protein (MCP) and the host inhibitor of apoptosis protein (SeIAP). Coimmunoprecipitation assays revealed interaction between SeIAP and SeCasps, but this interaction was disturbed in ascovirus-infected cells. This study details the in vitro infection process of ascovirus, indicating the utilization of pyroptosis for antiapoptosis cytopathology. IMPORTANCE Clarifying the relationship between different types of viral infections and host regulation of cell death (RCD) can provide insights into the interaction between viruses and host cells. Ascoviruses are insect-specific viruses with apoptosis-utilizing-like infection cytopathology. However, RCD does not only include apoptosis, and while in our previous transmission electron microscopic observations, ascovirus-infected cells did not show typical apoptotic characteristics (unpublished data), in this study, they did show increased membrane permeability. These results indicate that the cytopathology of ascovirus infection is a complex process in which the virus manipulates host RCD. The RCD of insect cells is quite different from that of mammals, and studies on the former are many fewer than those on the latter, especially in the case of RCD in lepidopteran insects. Our results will lay a foundation for understanding the RCD of lepidopteran insects and its function in the process of insect virus infection.https://journals.asm.org/doi/10.1128/mbio.03119-22regulated cell deathascovirusapoptosispyroptosisHeliothis virescens ascovirus 3h |
| spellingShingle | Huan Yu Jin-Rong Li Hua-Yan Xiao Sheng-Kai Cao Bin Chen Ni Li Gong Chen Guo-Hua Huang Apoptosis or Antiapoptosis? Interrupted Regulated Cell Death of Host Cells by Ascovirus Infection In Vitro mBio regulated cell death ascovirus apoptosis pyroptosis Heliothis virescens ascovirus 3h |
| title | Apoptosis or Antiapoptosis? Interrupted Regulated Cell Death of Host Cells by Ascovirus Infection In Vitro |
| title_full | Apoptosis or Antiapoptosis? Interrupted Regulated Cell Death of Host Cells by Ascovirus Infection In Vitro |
| title_fullStr | Apoptosis or Antiapoptosis? Interrupted Regulated Cell Death of Host Cells by Ascovirus Infection In Vitro |
| title_full_unstemmed | Apoptosis or Antiapoptosis? Interrupted Regulated Cell Death of Host Cells by Ascovirus Infection In Vitro |
| title_short | Apoptosis or Antiapoptosis? Interrupted Regulated Cell Death of Host Cells by Ascovirus Infection In Vitro |
| title_sort | apoptosis or antiapoptosis interrupted regulated cell death of host cells by ascovirus infection in vitro |
| topic | regulated cell death ascovirus apoptosis pyroptosis Heliothis virescens ascovirus 3h |
| url | https://journals.asm.org/doi/10.1128/mbio.03119-22 |
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