Proposed mechanism for VZV ORF20 RHIM during VZV infection.
Upon VZV infection of a host cell the viral DNA is transported to the nucleus with some potentially leaked into the cytoplasm. Viral DNA is then transcribed into RNA and exported from the nucleus. ZBP1 can sense either VZV RNA or DNA and then via RHIM:RHIM interactions activate RIPK3 to drive apoptosis. However, the ORF20 RHIM, either from incoming viral capsids, or following de novo synthesis can interact with ZBP1 to prevent it driving apoptosis and thus prolong the survival of the infected cell to allow for the complete viral replication cycle to occur.