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. Author manuscript; available in PMC: 2017 Dec 1.
Published in final edited form as: J Med Virol. 2016 May 13;88(12):2025–2037. doi: 10.1002/jmv.24569

Table 1.

Antiviral Function Viral Evasion/Proviral Function
Non-Immune Cells
Hepatocyte

  1. Induce ISGs, IFN (type III>I) via RIG-I or MDA5/MAVS pathway or TLR3 upon recognition of HCV PAMPs in infected cells.

  2. Induce ISGs via IFN-Jak-STAT signaling.

  1. Core and NS5A: Inhibit Jak-STAT signaling pathway.

  2. NS3/4A: Disrupt RLHs and TLR3 signaling by cleaving MAVS.

  3. NS4B: Interfere RIG-I signaling through STING inhibition.
Cholangiocyte May play a role in inflammatory cytokines production by recognizing
HCV PAMPs via TLRs.
HSC

  1. Produce antiviral cytokines by recognizing HCV via TLRs.

  2. The source of retinol (vitamin A), which support antiviral ISGs production in hepatocytes.
LSEC

  1. Recognize HCV via PRRs (both RIG-I like helicases and TLRs).

  2. Likely serves as antigen presenting cell.

  3. Production of type I/III IFN and antiviral exosomes.

  1. Use L-/DC-SIGN to transport virion to space of Disse.

  2. BMP4 enhances HCV replication in hepatocytes.

  3. Support expression of LDL-R in hepatocytes(co-receptor of HCV entry)
Innate Immune Cells
Kupffer cell
/Macrophage

  1. Produce inflammatory cytokines by recognizing HCV PAMPs via TLRs.

    • -

      HCV core and NS3 proteins by TLR2/TLR1 and TLR2/TLR6 heterodimer complex.

    • -

      Phagocytosed HCV virion stimulates TLR7/8, result in NLRP3 dependent inflammasomes.

  2. Possibly plays a role in hepatic inflammation by phagocytosis of apoptotic body, DAMPs, or exosomes from infected cells.

  1. TNF-α upregulate OCLN and CD81 in hepatocytes.

  2. Core and NS5A: Block TLR signaling pathways.
DC

  1. Myeloid DC1 (BDCA-1):

    • -

      Produce TNF-α and IL-10 via TLR2 activation by core or NS3 protein.

    • -

      Produce of IL-6,IL-1β, IL-12 and type I IFN via TLR3.

  2. Myeloid DC2 (BDCA-3)

    • -

      Produce type III IFN via TLR3.

  3. Plasmacytoid DC (BDCA-2)

    • -

      Produce type I IFN via TLR3, 7, 8, 9 upon phagocytosis of HCV particle or by engulfing exosomes containing PAMPs.

  1. Core and E1: Prohibit the maturation of DC.

  2. E2 binds to BDCA-1, CLRs, DCIR and inhibit production of type I IFN.
NK cell CD56brightCD3− cells
  • -

    Inhibition of viral infection by producing type II IFN and cell death-inducing molecules.

 E2 inhibit the activation of NKs via binding to CD81.