Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5.

Autor: Imbiakha B; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Ezzatpour S; Department of Microbiology, Cornell University, College of Agriculture and Life Sciences, Ithaca, NY, 14853, USA., Buchholz DW; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Sahler J; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Ye C; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Olarte-Castillo XA; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA.; James A. Baker Institute for Animal Health, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Zou A; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Kwas C; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., O'Hare K; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Choi A; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Adeleke RA; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Khomandiak S; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Goodman L; James A. Baker Institute for Animal Health, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA.; Department of Public & Ecosystem Health, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Jager MC; Department of Population Medicine and Diagnostic Sciences, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Whittaker GR; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA.; Department of Public & Ecosystem Health, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Martinez-Sobrido L; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., August A; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA., Aguilar HC; Department of Microbiology and Immunology, Cornell University, College of Veterinary Medicine, Ithaca, NY, 14853, USA.; Department of Microbiology, Cornell University, College of Agriculture and Life Sciences, Ithaca, NY, 14853, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 Sep 22; Vol. 9 (38), pp. eadj1736. Date of Electronic Publication: 2023 Sep 22.
DOI: 10.1126/sciadv.adj1736
Abstrakt: Pathology studies of SARS-CoV-2 Omicron variants of concern (VOC) are challenged by the lack of pathogenic animal models. While Omicron BA.1 and BA.2 replicate in K18-hACE2 transgenic mice, they cause minimal to negligible morbidity and mortality, and less is known about more recent Omicron VOC. Here, we show that in contrast to Omicron BA.1, BA.5-infected mice exhibited high levels of morbidity and mortality, correlating with higher early viral loads. Neither Omicron BA.1 nor BA.5 replicated in brains, unlike most prior VOC. Only Omicron BA.5-infected mice exhibited substantial weight loss, high pathology scores in lungs, and high levels of inflammatory cells and cytokines in bronchoalveolar lavage fluid, and 5- to 8-month-old mice exhibited 100% fatality. These results identify a rodent model for pathogenesis or antiviral countermeasure studies for circulating SARS-CoV-2 Omicron BA.5. Further, differences in morbidity and mortality between Omicron BA.1 and BA.5 provide a model for understanding viral determinants of pathogenicity.
Databáze: MEDLINE
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