Modeling the contribution of coronavirus cellular tropism to viral pathogenesis

NIH Pandemic-Era Grants

Pandemic Era Grants

2023

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Principal Investigator: Beverly H Koller
Organization: UNIV OF NORTH CAROLINA CHAPEL HILL
Fiscal Year: 2023
Award: $233,250
Funding agency: National Institute of Allergy and Infectious Diseases

Summary
The cell and tissue tropism of viruses is defined as the capacity of a virus to infect
specific cells and tissues and is determined by both viral and cellular factors. An
important factor for initiation of infection is cell entry, which is dependent on the ability of
the virus to dock with its cognitive receptor. A growing understanding of species
differences in ACE2 structure and, perhaps more importantly, in tissue specific patterns
of expression has underscored the potential limitations in the use of mouse models for
the study of disease pathogenesis of coronaviruses such as SARS-CoV-2 that rely on
ACE2 for cellular entry. We propose to implement a strategy for the rapid generation of
mouse models in which human ACE2 expression is limited to individual or multiple
airway epithelial populations. Using these lines, we will examine the impact of the
cellular pattern of ACE2 expression in the respiratory tract on the sequence of events
following exposure to SARS-CoV2 coronavirus.

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coronavirus 2><SARSCoV2><Severe Acute Respiratory Coronavirus><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 exposure><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Start Codon><Structure><Structure of respiratory epithelium><Study models><Susceptibility><System><Therapeutic><Therapeutic Intervention><Tissues><Transgenic Mice><Transgenic Organisms><Translation Initiation Factor><Translational Initiation Factor><Tropism><Type II Cell><Type II Epithelial Receptor Cell><Type II Pneumocyte><Validation><Viral><Viral Diseases><Viral Pathogenesis><Virus><Virus Diseases><Virus Replication><Wuhan coronavirus><airway epithelium><alveolar type II cell><angiotensin converting enzyme 2><angiotensin converting enzyme II><apical membrane><bacteriophage P1 recombinase Cre><cell type><clinical relevance><clinically relevant><corona virus><corona virus disease 2019><corona virus emergence><coronavirus disease 2019><coronavirus disease 2019 exposure><coronavirus disease 2019 infection><coronavirus disease 2019 monitoring><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus emergence><coronavirus infectious disease-19><develop a vaccine><develop vaccines><development of a vaccine><developmental><disease of the lung><disease severity><disorder of the lung><emergent CoV><emergent corona virus><emergent coronavirus><emerging CoV><emerging corona virus><emerging coronavirus><enhancer cassette><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><expression cassette><gene cassette><genetic cassette><hCoV19><host response><immune system response><immunoresponse><in vivo Model><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><integration cassette><intervention therapy><knockin><lung disorder><lung function><male><model design><mouse development><mouse model><murine model><nCoV><nCoV2><new CoV><new corona virus><new coronavirus><novel CoV><novel corona virus><novel coronavirus><pathogen><promoter><promoter cassette><promotor><protection pathway><protective pathway><pulmonary><pulmonary function><receptor><reporter cassette><resistance cassette><respiratory tract epithelium><restoration><selectable cassette><selection cassette><severe acute respiratory syndrome coronavirus 2 monitoring><severe acute respiratory syndrome-CoV><social role><species difference><stop cassette><tissue tropism><tool><transcription cassette><transcriptional cassette><transgene cassette><transgenic><vaccine development><validations><viral infection><viral multiplication><viral replication><virus infection><virus multiplication><virus pathogenesis><virus tropism><virus-induced disease>