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CCC DNA

Figure 1. New cells. Nucleos(t)ide analogs. Golgi. ER. CCC DNA. HBV mRNA. Figure 2. The virus. The hepatocytes. Infected cells Long half-life. CCC DNA long half-life. Viral polymerase error rate mutations. Viral persistence. Selective pressure Antivirals Immune response

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CCC DNA

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  1. Figure 1 New cells Nucleos(t)ide analogs Golgi ER CCC DNA HBV mRNA

  2. Figure 2 The virus The hepatocytes Infected cells Long half-life CCC DNA long half-life Viral polymerase error rate mutations Viral persistence Selective pressure Antivirals Immune response Others Replication space Mutant fitness The host Selection of escape mutants

  3. Figure 3 G T A A 1. protein-RNA complex Hsp90 P O L 2. priming of reverse transcription p23 penciclovir entecavir  PMEA DAPD pregenome 5' 3. translocation 3TC, FTC, LFd4C POL . . . C . . .A A T G (-) DNA 4. elongation AAA pregenome 3' DR1 5. DNA dependent DNA polymerase activity : (+) strand DNA synthesis (+) DNA L-FMAU

  4. Figure 4 spacer Pol/RT RNaseH Terminal protein 845 a.a. 1 183 349 692 (rt1) (rt 344) YMDD GVGLSPFLLA II(F) A B C D E I(G) V173L L180M M204I/V Lamivudine / Emtricitabine A181V N236T Adefovir T184G S202I M250V Entecavir M204I Telbivudine Famciclovir L180M

  5. ADEFOVIR Figure 5 Wild type v LAMIVUDINE Lam-R ADF-R Lam + ADF -R Low Frequency ??

  6. Table 1

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