# Transcriptome Analysis Reveals Host Peripheral Blood Mononuclear Cells Response to Mpox Virus Infection

## TL;DR

This study explores how the immune system in rabbits responds to mpox virus infection by analyzing changes in gene activity in blood cells.

## Contribution

The study identifies specific immune pathways and gene expression changes in PBMCs during acute and recovery phases of mpox infection in rabbits.

## Key findings

- MPXV infection alters PBMC transcriptomic profiles, with IL-1 response and pathogenic infection pathways enriched at 6 days post-infection.
- During recovery, T cell receptor signaling is enriched, and rabbits develop protective immunity with neutralizing antibodies.
- Common upregulated genes in rabbits and monkeys during acute infection are linked to the interferon pathway.

## Abstract

Mpox virus (MPXV), a member of the Orthopoxvirus genus in the Poxviridae family, has long been endemic in Africa. The interaction between MPXV infection and peripheral immune responses is of great significance. However, the activation of signaling pathways and molecular changes in peripheral blood mononuclear cells (PBMCs) following MPXV infection remain poorly understood. This study evaluated the transcriptomic profiles of rabbit PBMCs during the mpox acute and recovery phases. The results showed that MPXV infection significantly altered the transcriptomic profiles of PBMCs. At 6 days post-infection, pathways related to pathogenic infection and IL-1 response were enriched, while at 14 days post-infection, the T cell receptor signaling pathway was enriched. During the mpox acute phase, inflammatory cytokines in serum such as IL-1α, IL-1β, IL-8, and IL-21 were upregulated, while MMP-9 and NCAM-1 were downregulated. In rabbits and rhesus monkeys, key genes upregulated in common during the mpox acute period were associated with the interferon pathway (e.g., the ISG15, OAS, and IFIT families), while downregulated genes were related to B-cell activation and differentiation (e.g., the MS4A1 and FCRL families). Additionally, rabbits developed protective immunity against reinfection, with neutralizing antibodies effectively activated. These findings provide insights into the molecular characteristics of PBMCs changes in in vivo models of MPXV infection, and offer references for the diagnosis, vaccine development, and therapeutic research of mpox.