Abstract
Infection with the novel coronavirus, SARS-CoV-2, results in pneumonia and other respiratory symptoms as well as pathologies at diverse anatomical sites. An outstanding question is whether these diverse pathologies are due to replication of the virus in these anatomical compartments and how and when the virus reaches those sites. To answer these outstanding questions and study the spatiotemporal dynamics of SARS-CoV-2 infection a method for tracking viral spread in vivo is needed. We developed a novel, fluorescently labeled, antibody-based in vivo probe system using the anti-spike monoclonal antibody CR3022 and demonstrated that it could successfully identify sites of SARS-CoV-2 infection in a rhesus macaque model of COVID-19. Our results showed that the fluorescent signal from our antibody-based probe could differentiate whole lungs of macaques infected for 9 days from those infected for 2 or 3 days. Additionally, the probe signal corroborated the frequency and density of infected cells in individual tissue blocks from infected macaques. These results provide proof of concept for the use of in vivo antibody-based probes to study SARS-CoV-2 infection dynamics in rhesus macaques.
Highlights
Since its emergence in late 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread throughout the world causing a global pandemic of Coronavirus Disease 2019 (COVID19)
To prepare the monoclonal antibody (mAb) for use as an in vivo probe, the Fc portion was removed through pepsin digestion to eliminate any Fc mediated localization of the intact immunoglobulin G (IgG) in live animals (Figure 1A)
We have used this methodology in the past with simian immunodeficiency virus (SIV) infection, one concern was that unlike SIV, SARS-CoV-2 does not bud directly from the cell surface, likely leading to less spike protein being present on the cell membrane of infected cells in vivo [49, 50]
Summary
Since its emergence in late 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread throughout the world causing a global pandemic of Coronavirus Disease 2019 (COVID19). Limited studies have shown the presence of virus in tissues outside of the respiratory tract, but these studies have used autopsy tissue or biopsies from infected individuals [3, 4, 7, 12] These single time-point samples cannot be leveraged to understand the kinetics of how the infection spreads to these tissues. A better understanding of the spatiotemporal dynamics of SARS-CoV-2 infection would help to determine sites of viral persistence and elucidate the biology behind non-respiratory tract symptoms. Both a model system that closely recapitulates human disease and a way to track infection in vivo is needed to study these spatiotemporal dynamics
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