IFIX is a nuclear DNA sensor that is known to induce cytokine expression in response to both cytoplasmic DNA and foreign DNA in the nucleus. Here, we examine the concomitant nuclear and cytoplasmic proteome changes that are driven by IFIX during immune response to viral infection and transfection of viral DNA. Furthermore, we identify the posttranslational modifications present on the IFIX protein during HSV-1 infection.