Validation of a naturally-occurring animal model for SARS-CoV-2 infection

NIH Pandemic-Era Grants

Pandemic Era Grants

2021

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Principal Investigator: Craig Andrew Miller
Organization: OKLAHOMA STATE UNIVERSITY STILLWATER
Fiscal Year: 2021
Award: $240,655
Funding agency: National Institute of General Medical Sciences

The overall objective of this project is to validate mechanisms of viral fitness and immunopathogenesis during SARS-CoV-2 
infection in domestic cats to establish baselines for downstream translational studies. Major goals (specific aims) for this 
project are as follows: 
Aim 1. Evaluate in vivo infection kinetics and viral fitness of SARS-CoV-2 in the domestic cat. We will use droplet digital PCR 
(ddPCR) to quantify absolute copy numbers of SARS-CoV-2 RNA in blood, nasal swabs, and respiratory tissues in order to 
characterize viral replication kinetics during acute infection in domestic cats, and compare these changes with co-expression of 
viral antigen and ACE2 receptors in respiratory tissues (IHC). We will also use virus amplicon sequencing assembly to evaluate 
the potential for genetic divergence in the feline host (i.e. does the virus evolve during infection in domestic cats). 
Hypotheses: SARS-CoV-2 infects ACE2-expressing feline respiratory cells, resulting in progressive replication of genetically 
conserved virus elements and lesions analogous to human COVID-19 
Aim 2. Identify key factors of immune dysfunction contributing to COVID-19 disease progression. We will use scRNASeq, flow 
cytometry, and multiplex immunoassays to define shifts in the immune profile during acute SARS-CoV-2 infection. We will 
compare changes in immunological parameters with viral replication kinetics (Aim 1) and clinical disease progression in order 
to (i) define how perturbations of immune function impact clinical disease progression and (ii) identify novel 
immunomodulatory targets to guide more effective therapies or vaccine candidates. 
Hypothesis: Progression of severe COVID-19 in cats is analogous to human disease and correlated with (i) CD4+ and CD8+ T 
cell deficiencies and (ii) pro-inflammatory cytokine expression (IL-6, IL-1β, TNFα,)

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