# Single-Cell Sequencing Reveals the Immune Characteristics of Secondary Liver Injury Induced Indirectly by CHIKV Infection in Rhesus Macaques

## TL;DR

This study uses single-cell sequencing to show how CHIKV infection indirectly causes liver damage in rhesus macaques through immune cell activation.

## Contribution

The paper introduces a novel rhesus macaque model to study CHIKV-induced liver injury and reveals immune cell dynamics via single-cell RNA sequencing.

## Key findings

- Significant liver damage was observed despite no viral load in liver tissue.
- CD8+ T and NKT cells showed cytotoxic effects, while CD4+ T and memory T cells had regulatory roles.
- Macrophages exhibited increased phagocytosis and activation-related gene expression.

## Abstract

Chikungunya virus (CHIKV) is now prevalent in multiple regions worldwide, posing a serious threat to human health. In this study, we have successfully established a rhesus macaque model of Chikungunya virus infection. Notably, while no viral load was detected in liver tissue on day 7 post-infection, significant pathological damage was observed. Single-cell RNA sequencing of liver tissue revealed a reduction in B cells following infection. Among T cells, CD8+ T and NKT cells mediated major cytotoxic effects, whereas CD4+ T and memory T cells primarily exerted regulatory functions that further enhanced the activation of CD8+ T and NKT cells. In macrophages, inflammatory macrophages fc gamma R-mediated phagocytosis upregulated, with multiple key activation-related genes being highly upregulated. Furthermore, we observed that there might be a potential bidirectional activation effect between T cells and macrophages. These results indicate that CHIKV-induced indirect liver injury is likely mediated not only by the virus itself but also, in part, by the activation of hepatic immune cells.