Orthobunyaviruses: Epidemiology, innate immune escape, and intervention strategies

Orthobunyaviruses, including La Crosse virus (LACV), Oropouche virus (OROV), Schmallenberg virus (SBV), and Akabane virus (AKAV), pose substantial threats to global public health and livestock industries. This review focuses on the interplay between these viruses and the host immune systems, highlighting key mechanisms of viral entry and immune evasion. The viruses exploit vulnerabilities in host innate immunity, particularly through nonstructural protein NSs, which disrupts type I interferon signaling and transcriptional machinery. Additionally, this review delineates how host restriction factors counteract viral proliferation through compartmentalized defense mechanisms including BST-2 and MxA. The review also discusses antiviral strategies, including vaccines and inhibitors. Hence, this review synthesizes current knowledge on host recognition, immune evasion, and therapies for Orthobunyaviruses infections (focusing on LACV, OROV, AKAV, SBV) to guide targeted antiviral and broad-spectrum countermeasure development against emerging Orthobunyaviruses threats.