Screening Host Antiviral Proteins under the Enhanced Immune Responses Induced by a Variant Strain of Porcine Epidemic Diarrhea Virus
ABSTRACT While discussing the ideal candidates of viral restriction factor, the interferon (IFN) and interferon-stimulated genes (ISGs) could be considered potential targets. However, numerous viruses have evolved multiple strategies to modulate the host innate immune signaling for optimal infection...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-08-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00661-22 |
| _version_ | 1811337824814759936 |
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| author | Min Sun Zeyanqiu Yu Miao Luo Bin Li Zihao Pan Jiale Ma Huochun Yao |
| author_facet | Min Sun Zeyanqiu Yu Miao Luo Bin Li Zihao Pan Jiale Ma Huochun Yao |
| author_sort | Min Sun |
| collection | DOAJ |
| description | ABSTRACT While discussing the ideal candidates of viral restriction factor, the interferon (IFN) and interferon-stimulated genes (ISGs) could be considered potential targets. However, numerous viruses have evolved multiple strategies to modulate the host innate immune signaling for optimal infection, including the porcine epidemic diarrhea virus (PEDV), a coronavirus spreading widely around the world with high morbidity and mortality in piglets. The immunosuppression mediated by PEDV infection creates an impediment for studying the host-virus interactions and screening the antiviral ISGs. Here, the PEDV variant strain 85-7C40 was screened using the continuous passaging, which showed significantly attenuated viral replication compared with its parent on MARC-145 cells. The comparative transcriptome analysis (accession nos. SRR13154018 to SRR13154026) indicated that 85-7C40 infection led to enhanced immune response on MARC-145 cells, particularly to the IFN antiviral signaling, which mediated the stronger activation of numerous ISGs. Numerous ISGs activated by 85-7C40 showed antiviral effects against the wild-type strain infection, particularly the IFI44 (an ISG upregulated specifically by the 85-7C40 infection) and OASL (upregulated higher in 85-7C40 than 85-7-infected cells), exhibited powerful antiviral activity. IFI44 promoted the production of RIG-I, while the OASL interacted directly with RIG-I, and then they both activated the phosphorylation of STAT1, indicating that they restricted PEDV replication by positively regulating the type I IFN response. Our results provided insight into the ISGs with antiviral activity against PEDV infection and also expanded our understanding of the innate immune response to PEDV infection, which may promote the development of novel therapeutics. IMPORTANCE Host innate immune responses, particularly interferon (IFN) antiviral signaling, can activate diverse downstream ISGs to exert antiviral effects. However, porcine epidemic diarrhea virus (PEDV) infection has evolved multiple strategies to escape from this immune clearance. The immunosuppression mediated by PEDV infection creates an impediment for studying the host-virus interactions. We screened a PEDV variant strain, 85-7C40, which induced enhanced immune responses on MARC-145 cells and thus mediated the stronger activation of numerous ISGs. The laboratory-generated variant might induce inconsistent immune responses with a natural wild-type strain during infection, while numerous ISGs activated by 85-7C40 showed antiviral effects against the wild-type strain infection, particularly the IFI44 and OASL, restricted PEDV replication by positively regulating the type I IFN response. These findings were suggestive of the immune-enhanced variant being capable of using as an ideal viral model for screening the efficient antiviral proteins and elucidating the underlying mechanisms between PEDV and host innate immune responses. |
| first_indexed | 2024-04-13T18:00:33Z |
| format | Article |
| id | doaj.art-38461e991997472eb0bf4c5b7055505a |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-13T18:00:33Z |
| publishDate | 2022-08-01 |
| publisher | American Society for Microbiology |
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| series | Microbiology Spectrum |
| spelling | doaj.art-38461e991997472eb0bf4c5b7055505a2022-12-22T02:36:15ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-08-0110410.1128/spectrum.00661-22Screening Host Antiviral Proteins under the Enhanced Immune Responses Induced by a Variant Strain of Porcine Epidemic Diarrhea VirusMin Sun0Zeyanqiu Yu1Miao Luo2Bin Li3Zihao Pan4Jiale Ma5Huochun Yao6Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, ChinaCollege of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaCollege of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaInstitute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, ChinaCollege of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaCollege of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaCollege of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaABSTRACT While discussing the ideal candidates of viral restriction factor, the interferon (IFN) and interferon-stimulated genes (ISGs) could be considered potential targets. However, numerous viruses have evolved multiple strategies to modulate the host innate immune signaling for optimal infection, including the porcine epidemic diarrhea virus (PEDV), a coronavirus spreading widely around the world with high morbidity and mortality in piglets. The immunosuppression mediated by PEDV infection creates an impediment for studying the host-virus interactions and screening the antiviral ISGs. Here, the PEDV variant strain 85-7C40 was screened using the continuous passaging, which showed significantly attenuated viral replication compared with its parent on MARC-145 cells. The comparative transcriptome analysis (accession nos. SRR13154018 to SRR13154026) indicated that 85-7C40 infection led to enhanced immune response on MARC-145 cells, particularly to the IFN antiviral signaling, which mediated the stronger activation of numerous ISGs. Numerous ISGs activated by 85-7C40 showed antiviral effects against the wild-type strain infection, particularly the IFI44 (an ISG upregulated specifically by the 85-7C40 infection) and OASL (upregulated higher in 85-7C40 than 85-7-infected cells), exhibited powerful antiviral activity. IFI44 promoted the production of RIG-I, while the OASL interacted directly with RIG-I, and then they both activated the phosphorylation of STAT1, indicating that they restricted PEDV replication by positively regulating the type I IFN response. Our results provided insight into the ISGs with antiviral activity against PEDV infection and also expanded our understanding of the innate immune response to PEDV infection, which may promote the development of novel therapeutics. IMPORTANCE Host innate immune responses, particularly interferon (IFN) antiviral signaling, can activate diverse downstream ISGs to exert antiviral effects. However, porcine epidemic diarrhea virus (PEDV) infection has evolved multiple strategies to escape from this immune clearance. The immunosuppression mediated by PEDV infection creates an impediment for studying the host-virus interactions. We screened a PEDV variant strain, 85-7C40, which induced enhanced immune responses on MARC-145 cells and thus mediated the stronger activation of numerous ISGs. The laboratory-generated variant might induce inconsistent immune responses with a natural wild-type strain during infection, while numerous ISGs activated by 85-7C40 showed antiviral effects against the wild-type strain infection, particularly the IFI44 and OASL, restricted PEDV replication by positively regulating the type I IFN response. These findings were suggestive of the immune-enhanced variant being capable of using as an ideal viral model for screening the efficient antiviral proteins and elucidating the underlying mechanisms between PEDV and host innate immune responses.https://journals.asm.org/doi/10.1128/spectrum.00661-22porcine epidemic diarrhea virustranscriptomicsimmune-enhanced variantIFNIFI44OASL |
| spellingShingle | Min Sun Zeyanqiu Yu Miao Luo Bin Li Zihao Pan Jiale Ma Huochun Yao Screening Host Antiviral Proteins under the Enhanced Immune Responses Induced by a Variant Strain of Porcine Epidemic Diarrhea Virus Microbiology Spectrum porcine epidemic diarrhea virus transcriptomics immune-enhanced variant IFN IFI44 OASL |
| title | Screening Host Antiviral Proteins under the Enhanced Immune Responses Induced by a Variant Strain of Porcine Epidemic Diarrhea Virus |
| title_full | Screening Host Antiviral Proteins under the Enhanced Immune Responses Induced by a Variant Strain of Porcine Epidemic Diarrhea Virus |
| title_fullStr | Screening Host Antiviral Proteins under the Enhanced Immune Responses Induced by a Variant Strain of Porcine Epidemic Diarrhea Virus |
| title_full_unstemmed | Screening Host Antiviral Proteins under the Enhanced Immune Responses Induced by a Variant Strain of Porcine Epidemic Diarrhea Virus |
| title_short | Screening Host Antiviral Proteins under the Enhanced Immune Responses Induced by a Variant Strain of Porcine Epidemic Diarrhea Virus |
| title_sort | screening host antiviral proteins under the enhanced immune responses induced by a variant strain of porcine epidemic diarrhea virus |
| topic | porcine epidemic diarrhea virus transcriptomics immune-enhanced variant IFN IFI44 OASL |
| url | https://journals.asm.org/doi/10.1128/spectrum.00661-22 |
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