Figure 14. Schematic presentation of morphogenesis and intracellular transport of wt HSV-1 and Us3 deletion mutants (Us3-).

( A) In pathway 1, wt HSV-1 virions derived by budding at the INM are intraluminally transported from the perinuclear space (PNS) via ER-to-Golgi transitions or via ER-Golgi intermediate compartments (ERGIC), the kiss and run mechanism, into Golgi cisternae for packaging into transport vacuoles that delivers virions to the plasma membrane for exocytotic release into the extracellular space. In pathway 2, capsids released via impaired nuclear pores (NP) either bud at Golgi or vacuolar membranes into Golgi cisternae or vacuoles or are wrapped by Golgi membranes or endosomal membranes. Wrapping means budding at membranes concomitantly forming the viral envelope and the vacuolar membrane. The result is a concentric vacuole containing a single virion. ( B) In the absence of the Us3 gene, virions cannot be released from the PNS possibly because the intraluminal transportation route is impaired. Nevertheless, Us3 deletion mutants are infective. Nucleus to cytoplasm capsid translocation via impaired nuclear pores is inhibited. Budding into Golgi cisternae and wrapping at Golgi membranes is inhibited. 98% of enveloped virions have been shown to locate in the PNS ( Wild et al., 2015).