# Transcriptional and functional remodeling of lung-resident T cells and macrophages by Simian varicella virus infection

## TL;DR

This study explores how Simian varicella virus infection alters lung immune cells, revealing changes in macrophages and T cells during the acute phase.

## Contribution

The study provides new insights into the transcriptional and functional changes in lung-resident immune cells during SVV infection.

## Key findings

- SVV infection reduces alveolar macrophages while increasing antiviral macrophages and T cell activity.
- Infected T cells have higher viral transcripts than infected macrophages.
- Differential expression of metabolism-related genes suggests adaptations for viral replication.

## Abstract

Varicella zoster virus (VZV) causes varicella and can reactivate as herpes zoster, and both diseases present a significant burden worldwide. However, the mechanisms by which VZV establishes latency in the sensory ganglia and disseminates to these sites remain unclear.

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 the 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.