Virus spread and immune response following anterior chamber inoculation of HSV-1 Lacking the Beclin-binding domain (BBD)

•HSV-1 infection is antagonized by the Beclin-binding domain (BBD).•Lack of the BBD limits virus replication and retinal damage.•Lack of the BBD increases autophagy response and activation of NLRP3 inflammasome.•Increasing autophagy response induces a more rapid innate immune response.

The autophagy response induced by HSV-1 infection is antagonized by the Beclin-binding domain (BBD). The purpose of this study was to determine if lack of the BBD affects viral spread and immune response in the eyes and brain. Our results showed that lack of the BBD increases autophagy response and activation of NLRP3 inflammasome, which in turn induces a more rapid innate immune response mediated by macrophage/microglia and NK cells in the injected eye, limiting virus replication and retinal damage. We conclude that autophagy plays a role in controlling HSV-1 infection by more rapid induction of the innate immune response.