Biphasic modulation of the TLR7 signaling pathway in bovine alphaherpesvirus (BoAHV) infection of neural cells

Abstract

The study investigates the role of TLR7 in the modulation of the immune response during infection of neuronal cells by bovine alphaherpesvirus (BoAHV) types 1 and 5. TLR7 is essential for detecting viral RNA and activating immune pathways. In BoAHV-1 infection, TLR7 is upregulated early and persistently. In contrast, BoAHV-5 initially suppresses TLR7 expression, with a delayed upregulation at the end of the infectious cycle, reflecting the ability of the virus to evade early immune detection. Furthermore, BoAHV-1 induces a strong activation of MyD88 and NF-κB, leading to rapid viral replication, while BoAHV-5 triggers a weaker immune response, resulting in slower viral replication during the initial hours of infection. Additionally, BoAHV-1 progressively activates IRF-7 whereas BoAHV-5 shows delayed IRF-7 activation. Nevertheless, BoAHV-5 induces a strong IFNα/β response. The antiviral effect of the TLR7 agonist, Imiquimod was evident at the late phase of BoAHV-5 infection and it was mediated by IFN-β. These findings suggest that targeting TLR7 signaling could be a potential therapeutic approach to modulate immune responses and control viral replication. However, the effectiveness of TLR7 agonists like Imiquimod may vary depending on the virus type and its immune evasion strategies, highlighting the need for further research to explore other molecules in the TLR7 pathway.