Table 4.

Alphaherpesvirus-host interactions that exploit microtubule-based motors dynein and kinesin.

Virus	Viral Protein	Host-Cell Proteins/System	Role	Reference
HSV-1	pUL34	Intermediate chain of the dynein complex (IC-1a)	Pulldown experiments of infected Vero and HEp-2 cells with IC-1a (and reciprocal experiments) identified an interaction with pUL34. pUL34 localised to the nuclear membrane when expressed by a baculovirus vector, confirming the protein is involved in transport to the nuclear membrane in the viral context. pUL34 is not a structural protein [64] so unlikely to be involved in cytoplasmic viral capsid transport.	[140]
HSV-1	pUS11	Kinesin-1 (KIF5)	Residues 867–894 of ubiquitous human kinesin-1 bind to a C-terminal RNA-binding domain of tegument pUS11 as evidenced by pulldown assays. HSV-1 pUS11 has 63% homology to HSV-2 pUS11, with variation in the N-terminal half, so this interaction could prove to be transferable. Not confirmed in vivo and one study suggests pUS11 is not a structural tegument protein [64].	[141]
HSV-1	Tegument proteins	Dynein, dynactin, kinesin-1	Tegumented capsids (lacking outer tegument and envelopes) were capable of binding microtubule associated proteins (MAPs) sourced from pig brain cytosol. 10% of capsids tested by in vitro single particle analysis had bound dynein and kinesin-1 simultaneously, suggesting HSV-1 capsid transport is not directed by exclusive presence of either minus- or plus-ended motors. Inner tegument, pUL36 and pUL37, suggested as most likely to bind motors or recruit other tegument proteins that bind motors at this stage, especially with early findings that without pUL36, HSV-1 particles form but have reduced infectivity and a decreased ability to bind to and transport along microtubules [142].	[143]
PrV	pUL36	Dynein, dynactin	Immunoprecipitation of pUL36-transfected HEK293 cells showed that it interacts with dynein/dynactin and can drive transport in the absence of other viral proteins when transfected into Vero cells. pUL36 is capable of transporting viral capsid along microtubules in conjunction with capsid-binding pUL25. A large proline-rich domain in the pUL36 C-terminus contributes to the interaction.	[144]
HSV-1	pUL37	Dystonin/BPAG1	Tegument protein pUL37 recruits dystonin/BPAG1 in human foetal foreskin fibroblasts (HFFF2), which most likely functions to crosslink and stabilise microtubules, to facilitate viral capsid transport during viral entry. Plus-end directed transport is inhibited by dystonin depletion, providing evidence that pUL37-dystonin interaction is required for transport of capsids from the centrosome to the nucleus.	[145,146]
HSV-1	pUS9	Kinesin-1	Five arginine residues in the basic domain of envelope protein pUS9 bind host motor kinesin-1 as determined by truncation construct pulldown studies. This domain was shown to contribute to anterograde axonal transport in infected primary rat dorsal root ganglionic (DRG) neurons and a mouse zosteriform model.	[147]
PrV	pUS9	Kinesin-3 (KIF1A)	pUS9 was found to interact with kinesin-3 using GFP-Trap pulldown. This interaction was shown to mediate efficient axonal sorting and anterograde axonal transport of viral particles in primary rat superior cervical ganglion neurons [148].	[149]
HSV-1	pUL35 (VP26)	Dynein light chains Tctex1 and RP3	In vitro yeast two-hybrid evidence that capsid protein VP26 recruits these dynein light chains. Microinjection of HEp-2 cells with HSV-1 ± VP26 suggested VP26 was important for viral retrograde transport. Subsequent deletion studies in cell lines suggest this is a dispensable interaction [150,151].	[152]
HSV-2	pUL56	Kinesin-3 (KIF1A)	In vitro evidence that envelope protein pUL56 interacts with kinesin-3 with a C-terminal transmembrane domain important for this interaction in transfected Vero cells. Possible role in anterograde axonal transport. Shown in PrV to support virus dissemination in vivo in embryonic chick DRG and an infected mouse model but is dispensable for intra-axonal transport beyond the sorting barrier [153].	[154]