Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics

Guo, Zong Sheng; Lu, Binfeng; Guo, Zongbi; Giehl, Esther; Feist, Mathilde; Dai, Enyong; Liu, Weilin; Storkus, Walter J.; He, Yukai; Liu, Zuqiang; Bartlett, David L.

doi:10.1186/s40425-018-0495-7

Table 2 Vaccinia virus (VV) encodes multiple genes whose products modulate immune responses

From: Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics

Viral genes	Key function	Relevant findings	References
A41L	chemokine binding protein	Deletion of A41L enhances VV immunogenicity and vaccine efficacy	[175]
A44L	3beta-HSD enzyme (v3beta-HSD)	A44L promotes steroid synthesis	[41, 176]
A46R	TLR inhibitor and putative IL-1 antagonist	A46R is an inhibitor of the TLR4 signaling pathway	[41]
A49	Triggers Wnt signaling	A49 targets β-TrCP and thus affects multiple cellular pathways, including the NF-κB and Wnt signaling cascades	[40]
A52R	Putative inhibitor of TLR signaling	A52R targets Toll-like receptor signaling complexes to suppress host defense	[38]
A53R	Soluble TNF receptor	The gene deleted virus retains high immunogenicity but replication is attenuated	[177]
B5R	Inhibits complement	Anti-B5 (EV protein) antibody-directed cell lysis via complement is a powerful mechanism for clearance of infected cells	[148]
B8R	IFN-γ soluble receptor	B8R is a type II IFN binding protein	[36, 178]
B13R (SPI-2)	Inhibits IL-1β converting enzyme	B13R is a nonessential immune-modulating gene that has antiapoptotic and anti-inflammatory properties with sequence homology to serine protease inhibitors (serpins)	[179]
B15R	IL-1β soluble receptor	Deletion led to increased dendritic cell, natural killer cell, and neutrophil migration, as well as chemokine/cytokine expression	[36, 38]
B18R	IFN-α/β soluble receptor	B18R encodes a secreted decoy receptor with a broad antagonizing effect against type I IFNs. It is good for viral replication	[180]
C3L (VCP)	Complement control protein (VCP)	VCP modulates adaptive immune responses during infection	[181, 182]
C6	Binds to STA2 and inhibits type I IFN signaling	C6 is a dual function protein that inhibits the cellular responses to type I IFNs and as an inhibitor of IRF-3 activation	[183]
C7L	Antagonizes IRF1-induced antiviral activities	C7L inhibits antiviral activities induced by Type I interferons	[184, 185]
C12L	Binds and inhibits IL-18	C12L promotes virulence by reducing gamma interferon production and natural killer and T-cell activity	[41, 186]
E3L	Binds dsRNA to block PKR activation	E3 protein prevents the antiviral action of ISG15	[187]
F1L	Inhibits cytochrome C	F1L promotes virulence by inhibiting inflammasome activation	[188]
K1L	Inhibits NF-κB activation	K1L supports viral replication in human cells. Deletion of the gene led to a virus that is less pathogenic due to muted innate immune responses, yet still elicits protective immunity	[39]
K3L	The dsRNA-activated protein kinase (PKR) is inhibited by this pseudosubstrate inhibitor	K3L prevents phosphorylation of e1F2α	[189, 190]
K7R	Promotes histone methylation associated with heterochromatin association	K7R is a virulence gene; it inhibits the NF-κB pathway and thus the migration of neutrophil cells. It affects the acute immune response	[37, 38, 191, 192]
M1L	Associates with apoptosome	The current model is that M1L associates with and allows the formation of the apoptosome, but prevents apoptotic functions of the apoptosome	[193]
N1L	Inhibits NF-κB	N1L is a Bcl-2-like anti-apoptotic protein. It inhibits the NK cell response	[194]

Due to the limitation of the number of references that can be cited for this journal, not all relevant papers can be listed

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