Comparative RNA-seq analysis of Bovine parainfluenza virus type 3 and its V gene-deleted variant reveals that deletion of the V gene affects autophagy signaling.

Abstract

Bovine parainfluenza virus type 3 (BPIV3) is a major respiratory pathogen in cattle, with a substantial economic impact on the global livestock industry. The V protein, a nonstructural accessory protein expressed via RNA editing of the P gene, antagonizes canonical antiviral signaling. However, its additional role in promoting viral replication remains poorly defined. Here, we demonstrate that the BPIV3 V protein significantly enhances viral replication via a novel autophagy-dependent mechanism. Using a reverse genetics system, we generated a V-gene deletion mutant (rBPIV3-ΔV). Comparative transcriptomic (RNA-seq) analysis of cells infected with wild-type BPIV3 and rBPIV3-ΔV revealed that the V protein specifically modulates host autophagy signaling. We confirmed key differentially expressed genes using real-time quantitative PCR and identified the V protein as the essential viral factor driving BPIV3-induced autophagy. Collectively, our transcriptomic data delineate the molecular differences underlying the attenuated replication of rBPIV3-ΔV and establish that the V protein exploits the autophagy pathway to facilitate viral propagation in vitro. This finding provides a crucial theoretical advance in understanding BPIV3 pathogenesis and reveals potential targets for the development of novel antivirals and vaccines.