Table 1.

Alphaherpesvirus-host interactions that regulate actin dynamics.

Virus	Viral Protein	Host Cell Proteins/System	Role	Reference
HSV-1 HSV-2	gD	Nectins	gD binds to host-cell receptor nectin. Nectins regulate actin reorganisation by activating remodelling proteins like Ras/Rho GTPases (Rap1, Cdc42, Rac1). Rac1/Cdc42 have been implicated in signalling during early HSV-1 infection. However, evidence has shown that Rac1 and Cdc42 signalling does not occur in infected keratinocytes [75].	[76,77,78]
HSV-1	gD	Likely nectin-1/HVEM	Following viral binding, there is activation of Cdc42 and RhoA, causing filopodium-like protrusions in corneal fibroblasts and nectin-1-expressing Chinese hamster ovary (CHO) cells. Virus associates with these protrusions during viral entry and actin depolymerisation drugs inhibit viral entry. Also observed in a zebrafish model.	[78,79]
HSV-1	Unknown	Na+/H+ exchangers (NHE), p21-activated kinases	Internalisation of HSV-1 relies on the activity of these NHEs on the plasma membrane of Vero, HeLa, HEp-2 and PtK2 cells. These are known to be involved in macropinocytosis, an actin-dependent endocytic process which takes up extracellular fluid and macromolecules. This process can withstand the endocytosis of large structures (0.2–5 μm) which a large pathogen like HSV-1 can exploit.	[80]
HSV-2 PrV	pUS3	PAK1/PAK2	pUS3 directly phosphorylates group A p21-activated kinases (PAKs). Actin stress fibre disassembly during PrV infection of mouse embryonic fibroblast (MEF) and swine testicle (ST) cells is pUS3-mediated and requires PAK2. Cellular projections are mediated by PAK1. pUS3 kinase activity leads to protein kinase A-dependent phosphorylation of RhoA in ST cells; this subverts the antagonistic RhoA and Cdc42/Rac1/PAK signalling cascades for actin remodelling.	[81,82,83,84,85,86]