Abstract
Both the development of the mammalian innate immune system and the antagonistic strategies acquired by alphaherpesviruses to dismantle it have been shaped by co-evolving virus-host interactions over millions of years. Here, we review mechanisms employed by mammalian cells to detect pathogen molecules, such as viral glycoproteins and nucleic acids, and induce innate immune signaling upon infection with alphaherpesviruses. We further explore strategies acquired by these viruses to bypass immune detection and activation, thereby supporting virus replication and spread. Finally, we discuss the contributions of advanced 'omics' and microscopy methods to these discoveries in immune signaling and highlight emerging technologies that can help to further our understanding of the dynamic interplay between host innate immune responses and virus immune evasion.