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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1408212

Transcriptional and functional remodeling of lung-resident T cells and macrophages by Simian Varicella Virus infection

Provisionally accepted
Brianna M. Doratt Brianna M. Doratt Delphine C. Malherbe Delphine C. Malherbe Ilhem Messaoudi Ilhem Messaoudi *
  • Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, Kentucky, United States

The final, formatted version of the article will be published soon.

    Varicella zoster virus (VZV) causes varicella and can reactivate as herpes zoster, both diseases present a significant burden worldwide. However, the mechanisms by which VZV establishes latency in sensory ganglia and disseminates to these sites remain unclear. Here, we combined a single cell sequencing approach and a well-established rhesus macaque experimental model using Simian varicella virus (SVV), which recapitulates the VZV infection in humans, to define the acute immune response to SVV in the lung as well as compare the transcriptome of infected and bystander lung-resident T cells and macrophages. Our analysis showed a decrease in frequency of alveolar macrophages concomitant with an increase in that of infiltrating macrophages expressing antiviral genes as well as proliferating T cells, effector CD8 T cells, and T cells expressing granzyme A (GZMA) shortly after infection. Moreover, infected T cells harbored higher numbers of viral transcripts compared to infected macrophages. Furthermore, genes associated with cellular metabolism (glycolysis and oxidative phosphorylation) showed differential expression, in infected cells suggesting adaptations to support viral replication. Overall, these data suggest that SVV infection remodels the transcriptome of bystander and infected lung-resident T cells and macrophages.

    Keywords: varicella zoster virus, simian varicella virus, Bystander cells, T cells, Macrophages, Lung, Acute viral infection, Single-cell transcriptome analysis

    Received: 27 Mar 2024; Accepted: 08 May 2024.

    Copyright: © 2024 Doratt, Malherbe and Messaoudi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ilhem Messaoudi, Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, 40506, Kentucky, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.