Table 1 Interaction of HCV proteins with PRRs

Core

TLR2

Induction of TLR2 homotolerance

Serum derived or recombinant core does not recognize TLR2

Induction of TLR2 crosstolerance with TLR4

Monomeric Core recognize core

TLR1 or TLR6 are used as coreceptors with TLR2

Net Effect = Delayed Immune Response

NS3/4A

TLR3

Block TRIF and Cadif (adapter proteins) in down-stream signaling pathways of TLR3 and RIG-1 respectively

TLR3 and RIG-1 pathways are not activated until sufficient amount of dsRNA is produced, thus delaying innate immune response

RIG-1

TLR2

TLR1 or TLR6 are used as coreceptors with TLR2

NS5A

TLR4

Increases TLR4 expressions

Block MyD88 (adapter protein) of TLR4 signaling pathway

Also downregulates the expression of NFkB, MD2, CD14 and IRF3

Increases secretion of IL6, IFNβ, TGFβ and IL10

Suppresses IL12 secretion