MGF110-2L deletion prevents IFN-I and inflammatory response resulting in attenuation and protection against virulent ASFV.
African swine fever virus (ASFV) encodes numerous multigene family (MGF) proteins whose individual contributions to virulence and immune modulation remain poorly understood. Here, we characterize the role of MGF110-2L in shaping innate immunity and disease outcome in vivo. Deletion of MGF110-2L from the virulent Arm/07/CBM/c2 isolate markedly attenuated clinical disease and conferred complete protection against homologous challenge. In macrophages, the MGF110-2L-deficient recombinant induced enhanced type I IFN responses, consistent with a role for MGF110-2L in antagonizing antiviral signaling. However, transcriptomic profiling of peripheral blood mononuclear cells revealed that the absence of MGF110-2L prevents the excessive IFN and inflammatory hyperactivation triggered by the parental virus in vivo, establishing a controlled antiviral program associated with reduced pathology. These findings identify MGF110-2L as a functional virulence factor that drives dysregulated innate immune responses during ASFV infection. Our work advances the molecular understanding of ASFV–host interactions and highlights the contribution of MGF110-2L protein to immune evasion and pathogenesis.
African swine fever virus (ASFV) encodes numerous multigene family (MGF) proteins whose individual contributions to virulence and immune modulation remain poorly understood. Here, we characterize the role of MGF110-2L in shaping innate immunity and disease outcome in vivo. Deletion of MGF110-2L from the virulent Arm/07/CBM/c2 isolate markedly attenuated clinical disease and conferred complete protection against homologous challenge. In macrophages, the MGF110-2L-deficient recombinant induced enhanced type I IFN responses, consistent with a role for MGF110-2L in antagonizing antiviral signaling. However, transcriptomic profiling of peripheral blood mononuclear cells revealed that the absence of MGF110-2L prevents the excessive IFN and inflammatory hyperactivation triggered by the parental virus in vivo, establishing a controlled antiviral program associated with reduced pathology. These findings identify MGF110-2L as a functional virulence factor that drives dysregulated innate immune responses during ASFV infection. Our work advances the molecular understanding of ASFV–host interactions and highlights the contribution of MGF110-2L protein to immune evasion and pathogenesis.
Centro Biologia Molecular Severo Ochoa (CBMSO)