FIGURE 2.

HSV-1 replication cycle. The virus attaches via glycoproteins to cellular receptors. It enters the cells via the fusion of the viral envelope with the plasma membrane or endocytosis. The de-enveloped nucleocapsid is transported to the nuclear pores, and the viral DNA (vDNA) is ejected into the nucleus. The viral genes are transcribed in a temporal cascade: immediate early (IE), early (E), and late (L) proteins. IE protein expression is turned on by the virion-associated protein VP16. E proteins require IE protein synthesis for their expression and play critical roles in triggering vDNA replication. The hypothesized mechanisms underlying vDNA replication involve theta replication followed by rolling circle replication. L protein expression is dependent on vDNA replication. The capsid is assembled at sites adjacent to vDNA replication compartments, permitting the insertion of vDNA into the capsid. The nucleocapsid buds through the nuclear membrane, is transported through the cytoplasm, and fuses with the plasma membrane. During this journey, the nucleocapsid acquires tegument and envelope proteins. The release of mature progeny virions promotes attachment to new cells, and the cycle continues. Adapted with permission from Alandijany (2018).