# Temporal Dynamics of Cytokine, Leukocyte, and Whole Blood Transcriptome Profiles of Pigs Infected with African Swine Fever Virus

## TL;DR

This study tracks immune responses in pigs infected with African swine fever virus, revealing how inflammation and cell changes lead to disease progression.

## Contribution

The study provides a detailed temporal analysis of immune responses during acute African swine fever in pigs.

## Key findings

- Plasma levels of interferons and cytokines rise rapidly during acute ASF, coinciding with clinical disease and viral spread.
- Lymphocyte and NK cell populations decline progressively, while macrophage levels spike before death.
- Transcriptomic analysis shows early downregulation of translation and later upregulation of antiviral processes.

## Abstract

African swine fever virus (ASFV) is an important transboundary animal pathogen with significant impacts on the global swine industry. Overwhelming proinflammatory responses are a major virulence mechanism for ASFV, but the dynamics of these changes during clinical disease are not completely understood. We constructed a detailed portrait of the innate immune responses during acute African swine fever (ASF) at the cellular, transcriptomic, and cytokine levels. Samples serially obtained from infected piglets show that progression of acute ASF is characterized by rapid increases in plasma type I interferons, TNF-α, IL-12p40, and IL-10, which coincide with the manifestation of clinical disease and viral DNAemia. Lymphocytes and natural killer (NK) cells progressively declined, with fluctuations in B cell, CD8+ T cell, and CD4+/CD8+ T cell populations. Blood monocytes and macrophages were highly variable throughout infection, with an abrupt spike in CD203+ mature macrophages immediately prior to death. Transcriptomic analysis of blood showed downregulation of cellular translation as early as 1 day post-challenge (DPC) and significant upregulation of antiviral immune processes at 5 DPC and 7 DPC, which overlapped with the onset of clinical disease. Together, these results present a detailed delineation of fatal ASF which involves an initial infection and damage of susceptible myeloid cells prior to symptomatic disease characterized by pro-inflammatory immune responses, lymphoid depletion, and clinical deterioration.