Characterization of SARS-CoV-2 infection in primary human lower respiratory tract and small intestinal tissue models

Authors

• E Price
• EM Pugacheva
• YJ Ji
• D Loukinov
• V Lobanenkov

Abstract

While the global and public health emergencies were declared ended in May 2023, there is still concern surrounding both new acute SARS-CoV-2 infections, variant emergence, and the role of persistent infections and symptoms (e.g. long COVID). Because of the continued spread and subvariant emergence, it is critical that the scientific community quickly assess the public impact and dangers of emerging SARS-CoV-2 variants, including changes in infectivity, disease burden, tissue tropism, drug sensitivity, and immunological escape. To achieve this goal, the Antiviral Program for Pandemics Advanced Models & Cell-Based Discovery Team at NCATS, in collaboration with the 3D Tissue Bioprinting Lab, are using human SARS-CoV-2 infected air liquid interface (ALI) primary human airway and alveolar tissues to monitor various infection parameters. In the work presented here, we have infected these tissues with early and current SARS-CoV-2 variants/subvariants and measured temporal and tissue specific 1) variant infectivity/replication, 2) transcriptomic changes, and 3) secreted cytokine responses, and 4) sensitivity to select approved anti-SARS-CoV-2 small molecules. In addition, we also established a long-term human gut infection model by SARS-CoV-2 and investigated variant-specific infectivity profiles in this model for up to 21 days after infection. During these 21 days, we measured sustained intracellular SARS-CoV-2 RNA levels, as well as investigated infectious virion production, tissue transcriptomic changes, and secreted cytokine responses over time.

Scientific Focus Area: Virology

This page was last updated on Monday, September 25, 2023