# Transmissible Gastroenteritis Virus Binding to Red Blood Cells Disrupts Iron Homeostasis and Promotes Viral Infection

## TL;DR

This study shows that TGEV virus binds to red blood cells, damages them, and disrupts iron balance, which may worsen viral infection in piglets.

## Contribution

The study reveals a novel role of red blood cells in TGEV infection by showing how viral binding leads to impaired oxygen transport and iron homeostasis.

## Key findings

- TGEV binds to red blood cells without replicating, causing membrane damage and reduced oxygen-carrying capacity.
- TGEV infection promotes macrophage-mediated phagocytosis of red blood cells and lowers serum iron levels.
- Impairment of red blood cells contributes to TGEV pathogenesis and suggests new diagnostic and therapeutic strategies.

## Abstract

Transmissible gastroenteritis virus (TGEV) is an enteric coronavirus, and numerous studies have focused on the interaction between TGEV and the intestinal tract. In our experiment, breathlessness was observed in TGEV-infected piglets, suggesting impaired oxygen uptake by RBCs. The effects of TGEV infection on red blood cells (RBCs) and its pathophysiological implications were explored. TGEV was found to bind to, but not replicate in, RBCs. TGEV binding to RBCs causes membrane structure damage, impairs oxygen-carrying capacity, promotes macrophage-mediated phagocytosis of damaged RBCs, and reduces serum iron levels, thereby facilitating viral infection. These findings highlight the importance of diagnostic technologies targeting RBCs and suggest new avenues for drug development and vaccine design for TGEV prevention. Further exploration of the mechanisms by which RBCs contribute to viral infection is warranted.

Red blood cells (RBCs) are essential for transporting oxygen from lungs to peripheral tissues. However, the impact of transmissible gastroenteritis virus (TGEV) infection on RBCs and its potential pathophysiological significance during disease progression remain largely unexplored. In this study, hematological analysis of TGEV-infected piglets revealed significant reduction in both RBC distribution width–coefficient of variation and RBC distribution width–standard deviation, alongside elevated pCO2 levels. Viral detection confirmed the presence of TGEV within RBCs from infected piglets. Further investigation demonstrated that TGEV could bind to, but not replicate in, RBCs. TGEV-bound RBCs exhibited crenated and impaired deformability, which were associated with reduced oxygen-carrying capacity. Additionally, TGEV infection promoted macrophage-mediated phagocytosis of RBCs and led to decreased serum iron levels, factors that might enhance TGEV infection. Collectively, these results demonstrated the involvement of RBCs in the progression of TGEV infection, providing new insights for the development of diagnostic and therapeutic strategies.