Impact of VHSV on CIITA-mediated MHCII expression and antigen presentation in largemouth bass.

Viral hemorrhagic septicemia virus (VHSV) infection poses a significant threat to fish immunity by evading antigen presentation. Our previous study indicated that VHSV inhibited the transcriptional activation of MHC class II (MHCII) to impair antigen presentation in vitro, but the underlying mechanisms remain unclear. Here, we cloned and characterized the class II major histocompatibility complex transactivator (CIITA) in largemouth bass (Micropterus salmoides), a key regulator of MHCII expression, demonstrating that it activates MHCII transcription and possesses antiviral properties against VHSV. Following VHSV infection, CIITA and its downstream target MHCII were significantly downregulated in vivo. Further analysis revealed that the VHSV N protein degrades CIITA, primarily via its H3 and FCH domains, thereby impairing MHCII expression and antigen presentation. This study uncovers a critical mechanism through which VHSV inhibits adaptive immunity in fish and provides a theoretical basis for developing live-attenuated VHSV vaccines.