LncRNA-MSTRG.16919.1通过TAK1/TAB1/TAB2/TAB3复合物调节MDBK细胞中BHV-1的增殖

Bovine herpesvirus type 1 (BHV-1) is the primary pathogen responsible for infectious rhinotracheitis in cattle, leading to significant economic losses in the cattle industry. Long non-coding RNAs (lncRNAs) are multifunctional transcriptional regulators that play a role in the regulation of host-virus-specific interactions. Our previous study found that lncRNA-MSTRG.16919.1 is highly expressed in BHV-1 infected MDBK cells. Functional assays showed that its silencing reduced viral DNA replication, downregulated transcription and protein expression of glycoproteins gB and gD, and decreased virion production, indicating that it promotes BHV-1 proliferation. Further investigation revealed that knockdown of this lncRNA reduced protein levels of TAB1, TAB2, TAB3, and TAK1. To validate the involvement of the TAK1/TABs complex, we overexpressed TAK1 or TAB2 in cells with lncRNA knockdown. Overexpression restored viral DNA synthesis, gB and gD expression, and virus titers, counteracting the suppression caused by lncRNA silencing. Moreover, TAK1 or TAB2 overexpression elevated protein levels of TAB3, TAB1, TAK1, NF-κB, and JNK. These results demonstrate that lncRNA-MSTRG.16919.1 facilitates BHV-1 replication by modulating the TAK1-TABs complex and activating the NF-κB pathway. These findings provide foundational insights for studying the function and regulatory mechanisms of lncRNA-MSTRG.16919.1 in organisms, and contribute to the understanding of the pathogenic mechanisms of BHV-1, aiding in the prevention and control of bovine respiratory diseases.