Single-cell transcriptomic profiling of bronchial lymph nodes reveals mechanisms of PRRSV escape from host adaptive immunity.

INTRODUCTION

Porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV), is characterized by impaired adaptive immune responses, including persistent viremia, delayed neutralizing antibody (nAb) development, and defective T-cell responses. However, the mechanisms by which PRRSV subverts adaptive immunity remain incompletely understood.

METHODS

We performed single-cell RNA sequencing of bronchial lymph nodes (BLNs) collected from piglets infected with the highly pathogenic PRRSV (HP-PRRSV) wild-type isolate HV or its attenuated derivative N29 to characterize immune cell composition, transcriptional programs, and intercellular communication associated with PRRSV infection.

RESULTS

HP-PRRSV HV infection reduced the proportions of multiple T-cell subsets, including naive T cells, proliferating T cells, and central memory T cells (Tcm), while increasing the proportion of B cells in BLNs. The infection also appeared to disrupt T-cell egress, potentially resulting in the accumulation of cytotoxic T lymphocytes (CTLs) within BLNs. In addition, HP-PRRSV HV impaired the crosstalk between T follicular helper cells and germinal center B cells, a key interaction required for antibody maturation, thereby potentially suppressing nAb production. Notably, we identified a previously unrecognized PRRSV-associated RAG1+ CD4+CD8+ double-positive (DP) T-cell subset with potential roles in lipid antigen recognition.

DISCUSSION: These findings suggest a multifaceted understanding of the PRRSV immune evasion mechanisms and may provide critical clues for vaccine design and antiviral strategies.