Fig. 10.

Model for INM scission by ESCRT-III. a In HSV-1-infected cells, ESCRT-III is recruited to INM sites, where HSV-1 capsids acquire a primary envelope that functions in INM scission to produce primary enveloped virions in the perinuclear space. Depletion of CHMP4 proteins impairs primary envelopment and produces an accumulation of primary enveloped virions in the invagination structures in the nucleus. Nuclear morphology is maintained by the lamina meshwork but HSV-1 infection dissociates nuclear lamina⁶. Thus, arrested virions might be mainly accumulated in the invagination structures derived from the INM. In normal (uninfected) human cells, ESCRT-III contributes to downregulate excess INM. This process might be similar to the vesicle-mediated nucleocytoplasmic transport of HSV-1 nucleocapsids. CHMP4 KO increases the INM proliferation in a manner independent of cell cycle. b Proposed model of vesicle-mediated nucleocytoplasmic transport of HSV-1 nucleocapsids. (i) Protein kinases recruited by the NEC induce local dissolution of the nuclear lamina to allow nucleocapsids access to the INM⁶. Host protein p32 contributes to the recruitment of protein kinase C⁶⁵. (ii) The NEC deforms the INM to wrap around the nucleocapsid. (iii) The NEC recruits ESCRT-III machinery via ALIX and mediates INM scission to complete primary envelopment. (iv) The de-envelopment process is still unclear, but a possible role of viral gB and gH together with host protein CD98hc, β1 integrin, and p32 has been reported^4,5,66. Phosphorylation of the NEC by the viral Us3 protein kinase promotes de-envelopment⁶⁷. The torsin/LULL1 complex may indirectly contribute to this step^68,69