Table 2.

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

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