Dataset Information

Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques.

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.

SUBMITTER: Madden PJ

PROVIDER: S-EPMC8739270 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Development of an <i>In Vivo</i> Probe to Track SARS-CoV-2 Infection in Rhesus Macaques.

Madden Patrick J PJ Arif Muhammad S MS Becker Mark E ME McRaven Michael D MD Carias Ann M AM Lorenzo-Redondo Ramon R Xiao Sixia S Midkiff Cecily C CC Blair Robert V RV Potter Elizabeth Lake EL Martin-Sancho Laura L Dodson Alan A Martinelli Elena E Todd John-Paul M JM Villinger Francois J FJ Chanda Sumit K SK Aye Pyone Pyone PP Roy Chad J CJ Roederer Mario M Lewis Mark G MG Veazey Ronald S RS Hope Thomas J TJ

Frontiers in immunology 20211224

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 <i>in vivo</i> is needed. We deve ...[more]

PMID: 35003140

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Project description:Severe coronavirus disease 2019 (COVID-19) has been associated with T cell lymphopenia, but no causal effect of T cell deficiency on disease severity has been established. To investigate the specific role of T cells in recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, we studied rhesus macaques that were depleted of either CD4+, CD8+, or both T cell subsets prior to infection. Peak virus loads were similar in all groups, but the resolution of virus in the T cell-depleted animals was slightly delayed compared to that in controls. The T cell-depleted groups developed virus-neutralizing antibody responses and class switched to IgG. When reinfected 6 weeks later, the T cell-depleted animals showed anamnestic immune responses characterized by rapid induction of high-titer virus-neutralizing antibodies, faster control of virus loads, and reduced clinical signs. These results indicate that while T cells play a role in the recovery of rhesus macaques from acute SARS-CoV-2 infections, their depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19. Neither primed CD4+ nor CD8+ T cells appeared critical for immunoglobulin class switching, the development of immunological memory, or protection from a second infection. IMPORTANCE Patients with severe COVID-19 often have decreased numbers of T cells, a cell type important in fighting most viral infections. However, it is not known whether the loss of T cells contributes to severe COVID-19 or is a consequence of it. We studied rhesus macaques, which develop only mild COVID-19, similar to most humans. Experimental depletion of T cells slightly prolonged their clearance of virus, but there was no increase in disease severity. Furthermore, they were able to develop protection from a second infection and produced antibodies capable of neutralizing the virus. They also developed immunological memory, which allows a much stronger and more rapid response upon a second infection. These results suggest that T cells are not critical for recovery from acute SARS-CoV-2 infections in this model and point toward B cell responses and antibodies as the essential mediators of protection from re-exposure.

Dataset Information

Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques.

Publications

Development of an <i>In Vivo</i> Probe to Track SARS-CoV-2 Infection in Rhesus Macaques.

Similar Datasets

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