Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant
ABSTRACT Diverse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged since the beginning of the COVID-19 pandemic. We investigated the immunological and pathological peculiarity of the SARS-CoV-2 beta variant of concern (VoC) compared to the ancestral strain. Comparati...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-10-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02371-22 |
| _version_ | 1828100400721428480 |
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| author | Sunhee Lee Gun Young Yoon Su Jin Lee Young-Chan Kwon Hyun Woo Moon Yu-Jin Kim Haesoo Kim Wooseong Lee Gi Uk Jeong Chonsaeng Kim Kyun-Do Kim Seong-Jun Kim Dae-Gyun Ahn |
| author_facet | Sunhee Lee Gun Young Yoon Su Jin Lee Young-Chan Kwon Hyun Woo Moon Yu-Jin Kim Haesoo Kim Wooseong Lee Gi Uk Jeong Chonsaeng Kim Kyun-Do Kim Seong-Jun Kim Dae-Gyun Ahn |
| author_sort | Sunhee Lee |
| collection | DOAJ |
| description | ABSTRACT Diverse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged since the beginning of the COVID-19 pandemic. We investigated the immunological and pathological peculiarity of the SARS-CoV-2 beta variant of concern (VoC) compared to the ancestral strain. Comparative analysis of phenotype and pathology revealed that the beta VoC induces slower disease progression and a prolonged presymptomatic period in the early stages of SARS-CoV-2 infection but ultimately causes sudden death in the late stages of infection in the K18-hACE2 mouse model. The beta VoC induced enhanced activation of CXCL1/2–CXCR2–NLRP3–IL-1β signal cascade accelerating neutrophil recruitment and lung pathology in beta variant-infected mice, as evidenced by multiple analyses of SARS-CoV-2-induced inflammatory cytokines and transcriptomes. CCL2 was one of the most highly secreted cytokines in the early stages of infection. Its blockade reduced virus-induced weight loss and delayed mortality. Our study provides a better understanding of the variant characteristics and need for treatment. IMPORTANCE Since the outbreak of COVID-19, diverse SARS-CoV-2 variants have been identified. These variants have different infectivity and transmissibility from the ancestral strains. However, underlying molecular mechanisms have not yet been fully elucidated. In our study, the beta variant showed distinct pathological conditions and cytokine release kinetics from an ancestral strain in a mouse model. It was associated with higher neutrophil recruitment by increased levels of CXCL1/2, CXCR2, and interleukin 1β (IL-1β) at a later stage of viral infection. Our study will provide a better understanding of SARS-CoV-2 pathogenesis. |
| first_indexed | 2024-04-11T08:29:16Z |
| format | Article |
| id | doaj.art-a86bfb004a884aca872b9971584b98c2 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-11T08:29:16Z |
| publishDate | 2022-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-a86bfb004a884aca872b9971584b98c22022-12-22T04:34:37ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-10-0110510.1128/spectrum.02371-22Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta VariantSunhee Lee0Gun Young Yoon1Su Jin Lee2Young-Chan Kwon3Hyun Woo Moon4Yu-Jin Kim5Haesoo Kim6Wooseong Lee7Gi Uk Jeong8Chonsaeng Kim9Kyun-Do Kim10Seong-Jun Kim11Dae-Gyun Ahn12Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaCenter for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South KoreaABSTRACT Diverse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged since the beginning of the COVID-19 pandemic. We investigated the immunological and pathological peculiarity of the SARS-CoV-2 beta variant of concern (VoC) compared to the ancestral strain. Comparative analysis of phenotype and pathology revealed that the beta VoC induces slower disease progression and a prolonged presymptomatic period in the early stages of SARS-CoV-2 infection but ultimately causes sudden death in the late stages of infection in the K18-hACE2 mouse model. The beta VoC induced enhanced activation of CXCL1/2–CXCR2–NLRP3–IL-1β signal cascade accelerating neutrophil recruitment and lung pathology in beta variant-infected mice, as evidenced by multiple analyses of SARS-CoV-2-induced inflammatory cytokines and transcriptomes. CCL2 was one of the most highly secreted cytokines in the early stages of infection. Its blockade reduced virus-induced weight loss and delayed mortality. Our study provides a better understanding of the variant characteristics and need for treatment. IMPORTANCE Since the outbreak of COVID-19, diverse SARS-CoV-2 variants have been identified. These variants have different infectivity and transmissibility from the ancestral strains. However, underlying molecular mechanisms have not yet been fully elucidated. In our study, the beta variant showed distinct pathological conditions and cytokine release kinetics from an ancestral strain in a mouse model. It was associated with higher neutrophil recruitment by increased levels of CXCL1/2, CXCR2, and interleukin 1β (IL-1β) at a later stage of viral infection. Our study will provide a better understanding of SARS-CoV-2 pathogenesis.https://journals.asm.org/doi/10.1128/spectrum.02371-22COVID-19SARS-CoV-2variantcytokinetranscriptome |
| spellingShingle | Sunhee Lee Gun Young Yoon Su Jin Lee Young-Chan Kwon Hyun Woo Moon Yu-Jin Kim Haesoo Kim Wooseong Lee Gi Uk Jeong Chonsaeng Kim Kyun-Do Kim Seong-Jun Kim Dae-Gyun Ahn Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant Microbiology Spectrum COVID-19 SARS-CoV-2 variant cytokine transcriptome |
| title | Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant |
| title_full | Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant |
| title_fullStr | Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant |
| title_full_unstemmed | Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant |
| title_short | Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant |
| title_sort | immunological and pathological peculiarity of severe acute respiratory syndrome coronavirus 2 beta variant |
| topic | COVID-19 SARS-CoV-2 variant cytokine transcriptome |
| url | https://journals.asm.org/doi/10.1128/spectrum.02371-22 |
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