196 Infect Dis Info, Vol. 23, No. 4, August 30, 2010 [ ] hepatitis C virus, 1 50% [ ] [ ] R512.63 [ ] A [ ] 1007-8134(2010)04-0196-05 Pathogenesis and drug therapy of hepatitis C QI Zhong-tian Department of Microbiology, Second Military Medical University, Shanghai Key Laboratory of Medical Biodefense, Shanghai 200443, China [Abstract] Hepatitis C virus () can affect host immune responses in several ways so that it can replicate persistently in hosts and lead to chronic infection. Currently standard therapy of the patients with chronic hepatitis C is the combination of pegylated interferon and ribavirin, but about 50% of the patients with genotype 1 infection cannot achieve sustained virologic response with the combination therapy and adverse reactions are found. In recent years, with the further research on replication and the function of non-structural proteins, there have been great advances in the development of virus-specific agents that have demonstrated promising efficacy on reducing viral replication in -infected patients. This review focuses on the current progress of the studies on cell entry, replication, escape from host innate and adaptive immune responses and new anti- agents in clinical trials. [Key words] hepatitis C virus; immune escape; virus replication; cell entry; drug therapy 1.7 6 HBV 50%~85% 10%~15% 1%~7% 1b pseudotype particles, pp [4] [1] RNA 9600 grown in cell culture, cc [5-6] 3010 10 1.1 PEG-IFN α RBV 1.1.1 sustained virologic response, SVR 1 SVR CD81 [7] SR-B1 [8-9] Clau- 4 50% [2-3] din-1 CLDN1 [10] Occludin [11] CD81 SR-B1 E2-CD81 GTPase 1 E2-CD81 CLDN1 Occludin ph [12] CLDN1 Occludin
Infect Dis Info, Vol. 23, No. 4, August 30, 2010 [13] 1.1.2 internal ribosome entry site, IRES 40S IFN T E2 3 7 NS3/4A NS5A NS5B E1 E2 p7 63 E2 RNA E2 [14] NS2-3 NS2 1/2 NS3 1/3 RNA double-stranded RNA-activated protein kinase, PKR E2 [15] NS2 PKR eukaryotic initiation factor, eif NS2 cc 2a E2 NS2 eif2a PKR eif2a [16] NS3-4A NS3 IFN N- 1/3 PKR NS3/4A C- 2/3 RNA NTP NS4A NS3 NS5A interferon regulatory factors, IRF -3 IFN IFN RNA NS5A IRF-3 NS5B RNA RNA RNA RNA RNA IRF-3 RNA IRF-3 Huh-7 CBP300 IFN [17] RNA NS3/4A 2 TRIF MAVS IRF- [19-20] 3 NF-κB RNA 1.2.2 RNA B [18] B NS5B RNA E2 1.1.3 27 1 NS2 RNA T cytotoxic T lymphocyte, CTL 1.2 major histocompatibility complex, MHC 1.2.1 T
198 Infect Dis Info, Vol. 23, No. 4, August 30, 2010 2.1 IFN RBV T 2.1.1 IFN IFN α MHC T CTL IFN 1.2.3 PEG-IFN α PEG-IFN α B T IFN PEG-IFN α IFN α B IFN α IFN α 1/3 Albumin-IFN α IFN α-2b 150 h 2.1.2 RBV IFN RBV 48 SVR 2 3 75%~ 80% 1 40%~50% RBV RBV RBV Levovirin RBV RBV 2 Viramidine RBV RBV PEG-IFN α RBV RBV 50 1 2.2 RBV 1 Figure 1 New anti- agents in clinical trials
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