The Battle between Virus and Host: Modulation of Toll-Like Receptor Signaling Pathways by Virus Infection

Table 1

Molecular mechanisms involved in modulation of host innate immune systems by viruses.

Virus/Virus protein	Host pathway	Function	Effect
RNA virus
Human immunodeficiency virus (HIV)
Nef	TCR-CD30	Inhibit NF-$\kappa$B and AP-1 activation	Inhibit T cell activation
	TLR4	Inhibit ERK activation (Dephosphorylation of ERK by induced MKP-1)	Suppress TNF-$\alpha$ production
Vpu	TLRs	Inhibit NF-$\kappa$B activation (Stabilize I$\kappa$B)	Suppress cytokine production
Tat		Activate NF-$\kappa$B (PKR-dependent)
Vpr		Activate NF-$\kappa$B	Enhance IL-6, IL-8, and IL-10 production
RNA40	TLR7/8	Activate IRF-7 mediated by MyD88	Activate pDCs
Human T-lymphotropic leukemia virus 1 (HTLV-1)
p30	TLR4	Suppress TLR4 expression (Suppress PU.1 fuction)	Suppress cytokine production
		Inhibit GSK3-$\beta$	Enhance IL-10 production
p12	TCR	Suppress phosphorylation of PLC-$\gamma$1 and Vav	Suppress T cell activation by DCs
Tax		Activate IKK (Bind to IKK$\gamma$)	Induce IL-2, IL-2R, GM-CSF, and IL-15
Hepatitis C virus (HCV)
NS3/4A	TLR3/4	Degrade TRIF	Suppress IFN-$\alpha /\beta$ production
			Suppress CD4^+ T cell activation by dysfunction of mDCs
NS5A	TLRs	Inhibit NF-$\kappa$B activation (Bind to MyD88)	Suppress cytokine production
		Inhibit JNK activation (Bind to TRAF2)	Suppress TNF pathway activation
core, NS3	TLR2	Activate MAP kinase pathway, NF-$\kappa$B, and AP-1	Dysfunction of pDCs by enhanced production of IL-10 and TNF-$\mathrm{\hspace{0.17em}\hspace{0.17em}}\alpha \mathrm{\hspace{0.17em}\hspace{0.17em}}$
Measles virus
N (?)			Suppress IL-12 production mediated by TLR4 in DCs (Suppress Th1 differentiation)
P	TLR2/4	Suppress NF-$\kappa$B and AP-1 activation (Upregulate host NF-$\kappa$B negative regulator A20)	Inhibit proinflammatory cytokine and chemokine production
HA	TLR2	Activate NF-$\kappa$B	Induce cytokine production
Influenza virus A
NS1	TLR3/7/9	Suppress of IRF3/7 activation	Inhibit IFN production in pDC
	TLR4	Suppress of NF-$\kappa$B and AP-1 activation	Suppress DC and T cell activation
	RIG-I	Suppress of IRF3/7 activation	Inhibit IFN production in mDC
SARS-coronavirus (SARS-CoV)
N		Activate AP-1; Bind  to NF-$\kappa$B  and  C/EBP binding motifs of IL-6 promoter	Induce IL-6 and COX-2
	promoter
Human respiratory syncytial virus (RSV)
G	TLR2/4/9	Suppress NF-$\kappa$B activation	Suppress cytokine production
F	TLR4	Activate NF-$\kappa$B	Induce IL-1, IL-6, IL-8, and RANTES
M2-1		Activate NF-$\kappa$B
?	TLR7/9		Suppress IFN production in pDC
NS1, NS2	TLR3/4, RIG-I	Suppress IRF3 activation	Suppress IFN production in mDC
Rotavirus
VP4		Activate NF-$\kappa$B; Suppress JNK (Bind  to  TRAF2)
DNA virus
Vaccinia virus
A46R	TLRs	Suppress NF-$\kappa$B activation (Bind to MyD88, TRAM, and TRIF)	Suppress cytokine production
A52R	TLRs	Suppress NF-$\kappa$B activation (Bind to IRAK2)	Suppress cytokine production
		Activate p38 MAPK and JNK (Bind to TRAF6)	Induce IL-10 production
N1L	TLRs	Suppress NF-$\kappa$B activation (Bind to IKK$\gamma$)	Suppress cytokine production
		Suppress IRF3 activation (Bind to TBK1)	Suppress IFN production
Adenovirus
RID	TLR4	Suppress NF-$\kappa$B and AP-1 activation	Suppress MCP-1 and IL-8 production
	TNF pathway	Suppress TNFR1 expression	Suppress MCP-1 and IL-8 production
capsid		Activate NF-$\kappa$B, ERK, and MAPK	Induce RANTES and IL-10
Herpes simplex virus (HSV)
virion	TLR2		Induce cytokine production
viral DNA	TLR9		Induce IFN production
Varicella-zoster virus
vrion	TLR2		Induce cytokine production
Human cytomegalovirus (HCMV)
late proteins	IL-1 system	Suppress NF-$\kappa$B activation (Inhibit site located upstream of MAP3K)
	TNF system	Suppress TNFR1 expression
gB/gH	TLR2/1	Activate NF-$\kappa$B	Produce proinflammatory cytokines
Epstein-Barr virus (EBV)
late protein		Suppress NF-$\kappa$B activation	Inhibit COX-2 activation
gp350/gp220	TLR2/CD21	Activate NF-$\kappa$B	Induce MCP-1 production
LMP-1		Activate p38 MAPK (TRAF6-dependent)	Suppress DC function by induced IL-10
Human herpesvirus 8 (HHV8)
vFLIP		Activate IKK
		(Bind to IKK$\gamma$)
RTA		Degrade IRF7 by proteasome system	Suppress IFN-$\alpha$/$\beta$ production
Hepatitis B virus
e antigen	IL-1 pathway	Activate NF-$\kappa$B	Induce cytokine
		(Bind to mIL-1RAcP)	production