Understanding variant-specific variations in neutrophil functional kinetics associated with SARS-CoV-2 infection in a feline animal model
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B579
Abstract ID: 5935
Presenting Author:
Sachithra Gunasekara , Graduate Teaching Assistant at Oklahoma State Univ. Ctr. for Hlth. Sci.
Abstract:
The intricate interplay between neutrophils and diverse SARS-CoV-2 variants offers insights into immunopathogenesis and potential therapeutic interventions in SARS-CoV-2 infection. Utilizing our COVID-19 feline model, we hypothesize that neutrophil dysregulation and the release of neutrophil extracellular traps (NETs) are highly strain-dependent in domestic cats. Specific-pathogen-free cats (n=8) were inoculated with SARS-CoV-2 (n=3 B.1.617.2/Delta; n=3 XBB.1.5/Omicron) or vehicle (n=2). Plasma, bronchoalveolar lavage, and lung tissues were collected over 5 days. Flow cytometric analysis of neutrophil subsets in blood, BAL, and tissues revealed functional and phenotypic changes (CXCR2+CXCR4-CCR5+) in Delta vs. Omicron vs. vehicle. Detection of NETs using MPO-DNA ELISA indicates significant elevations at 4dpi and 5dpi in the plasma and BAL of Delta and Omicron cats when compared to vehicle. Multiplex immunoassay conducted on BAL revealed significant elevation of pro-inflammatory cytokines including TNF-α, IL-8, and IL-18 in infected cats compared to vehicle favoring delta strain. RT-PCR and western blot on lung tissues utilizing three major markers of activated neutrophils and NETS (citrullinated histone 3, MPO, and neutrophil elastase) show marked expression in Delta cats vs Omicron and vehicle. These findings underscore the versatility of domestic cats as a translational model for developing targeted interventions based on variant-dependent neutrophil population dynamics.
Understanding variant-specific variations in neutrophil functional kinetics associated with SARS-CoV-2 infection in a feline animal model
Category
Poster and Podium (Block Symposium)