Kwun et al. (2002) discovered that the immediate early protein 0 of HSV-1 upregulates the activity of the cellular transcription factor AP-1, thereby enhancing the transactivation of HERV-K18 LTR. Additionally, herpesvirus infections, akin to influenza virus infections, induce IFN-mediated immune responses that can also trigger HERV-K18 sAg activation (Turcanova et al., 2009), potentially constituting a component of the host immune response. However, recent murine studies validating the sAg nature of HERV-K18 have failed to observe the onset of MS in animal models (Ilse et al., 2022). Here, SAG is linked to Herpesviridae infectious disease.