Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant.

Autor:	Lee S; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea., Yoon GY; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea.; Department of Immunology, College of Medicine, Konkuk University, Chungju, South Korea., Lee SJ; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea., Kwon YC; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea., Moon HW; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea., Kim YJ; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea., Kim H; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea., Lee W; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea., Jeong GU; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea., Kim C; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea., Kim KD; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea., Kim SJ; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea., Ahn DG; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technologygrid.29869.3c, Daejeon, South Korea.
Jazyk:	angličtina
Zdroj:	Microbiology spectrum [Microbiol Spectr] 2022 Oct 26; Vol. 10 (5), pp. e0237122. Date of Electronic Publication: 2022 Aug 25.
DOI:	10.1128/spectrum.02371-22
Abstrakt:	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.
Databáze:	MEDLINE
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