Immune Therapeutic Strategies in Chronic Hepatitis B Virus Infection: Virus or Inflammation Control?

1. BertolettiA, FerrariC (2012) Innate and adaptive immune responses in chronic hepatitis B virus infections: towards restoration of immune control of viral infection. Gut 61: 1754–1764.

2. KamataniY, WattanapokayakitS, OchiH, KawaguchiT, TakahashiA, et al. (2009) A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nat Genet 41: 591–595.

3. AsabeS, WielandSF, ChattopadhyayPK, RoedererM, EngleRE, et al. (2009) The size of the viral inoculum contributes to the outcome of hepatitis B virus infection. J Virol 83: 9652–9662.

4. PublicoverJ, GaggarA, NishimuraS, Van HornCM, GoodsellA, et al. (2013) Age-dependent hepatic lymphoid organization directs successful immunity to hepatitis B. J Clin Invest 123: 3728–3739.

5. WielandS, ThimmeR, PurcellRH, ChisariFV (2004) Genomic analysis of the host response to hepatitis B virus infection. Proc Natl Acad Sci U S A 101: 6669–6674.

6. LutgehetmannM, BornscheuerT, VolzT, AllweissL, BockmannJH, et al. (2011) Hepatitis B virus limits response of human hepatocytes to interferon-alpha in chimeric mice. Gastroenterology 140: 2074–2083.

7. TianY, ChenW-l, OuJ-hJ (2011) Effects of interferon-α/β on HBV replication determined by viral load. PLoS Pathog 7: e1002159 doi:10.1371/journal.ppat.1002159

8. ZeissigS, MurataK, SweetL, PublicoverJ, HuZ, et al. (2012) Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity. Nat Med 18: 1060–1068.

9. TangXZ, JoJ, TanAT, SandalovaE, ChiaA, et al. (2013) IL-7 licenses activation of human liver intrasinusoidal mucosal-associated invariant T cells. J Immunol 190: 3142–3152.

10. TuZ, BozorgzadehA, PierceRH, KurtisJ, CrispeIN, et al. (2008) TLR-dependent cross talk between human Kupffer cells and NK cells. J Exp Med 205: 233–244.

11. BoniC, FisicaroP, ValdattaC, AmadeiB, Di VincenzoP, et al. (2007) Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol 81: 4215–4225.

12. SchurichA, KhannaP, LopesAR, HanKJ, PeppaD, et al. (2011) Role of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 on apoptosis-Prone CD8 T cells in persistent hepatitis B virus infection. Hepatology 53: 1494–1503.

13. RaziorrouhB, SchrautW, GerlachT, NowackD, GrunerNH, et al. (2010) The immunoregulatory role of CD244 in chronic hepatitis B infection and its inhibitory potential on virus-specific CD8+ T-cell function. Hepatology 52: 1934–1947.

14. NebbiaG, PeppaD, SchurichA, KhannaP, SinghHD, et al. (2012) Upregulation of the Tim-3/galectin-9 pathway of T cell exhaustion in chronic hepatitis B virus infection. PLoS ONE 7: e47648 doi:10.1371/journal.pone.0047648

15. WuW, ShiY, LiS, ZhangY, LiuY, et al. (2012) Blockade of Tim-3 signaling restores the virus-specific CD8(+) T-cell response in patients with chronic hepatitis B. Eur J Immunol 42: 1180–1191.

16. MainiMK, SchurichA (2010) The molecular basis of the failed immune response in chronic HBV: therapeutic implications. J Hepatol 52: 616–619.

17. MichelML, DengQ, Mancini-BourgineM (2011) Therapeutic vaccines and immune-based therapies for the treatment of chronic hepatitis B: perspectives and challenges. J Hepatol 54: 1286–1296.

18. KosinskaAD, ZhangE, JohrdenL, LiuJ, SeizPL, et al. (2013) Combination of DNA prime–adenovirus boost immunization with entecavir elicits sustained control of chronic hepatitis B in the woodchuck model. PLoS Pathog 9: e1003391 doi:10.1371/journal.ppat.1003391

19. XuDZ, WangXY, ShenXL, GongGZ, RenH, et al. (2013) Results of a phase III clinical trial with an HBsAg-HBIG immunogenic complex therapeutic vaccine for chronic hepatitis B patients: experiences and findings. J Hepatol 59: 450–456.

20. HuangLR, WohlleberD, ReisingerF, JenneCN, ChengRL, et al. (2013) Intrahepatic myeloid-cell aggregates enable local proliferation of CD8(+) T cells and successful immunotherapy against chronic viral liver infection. Nat Immunol 14: 574–583.

21. IsogawaM, ChungJ, MurataY, KakimiK, ChisariFV (2013) CD40 activation rescues antiviral CD8+ T cells from PD-1-mediated exhaustion. PLoS Pathog 9: e1003490 doi:10.1371/journal.ppat.1003490

22. GehringAJ, HaniffaM, KennedyPT, HoZZ, BoniC, et al. (2013) Mobilizing monocytes to cross-present circulating viral antigen in chronic infection. J Clin Invest 123: 3766–3776.

23. Kidd-LjunggrenK, MiyakawaY, KiddAH (2002) Genetic variability in hepatitis B viruses. J Gen Virol 83: 1267–1280.

24. KohS, ShimasakiN, SuwanaruskR, HoZZ, ChiaA, et al. (2013) A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids 2: e114.

25. KrebsK, BottingerN, HuangLR, ChmielewskiM, ArzbergerS, et al. (2013) T cells expressing a chimeric antigen receptor that binds hepatitis b virus envelope proteins control virus replication in mice. Gastroenterology 145: 456–465.

26. SchietingerA, DelrowJJ, BasomRS, BlattmanJN, GreenbergPD (2012) Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state. Science 335: 723–727.

27. SunC, FuB, GaoY, LiaoX, SunR, et al. (2012) TGF-β1 down-regulation of NKG2D/DAP10 and 2B4/SAP expression on human NK cells contributes to HBV persistence. PLoS Pathog 8: e1002594 doi:10.1371/journal.ppat.1002594

28. DasA, HoareM, DaviesN, LopesAR, DunnC, et al. (2008) Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection. J Exp Med 205: 2111–2124.

29. XuD, FuJ, JinL, ZhangH, ZhouC, et al. (2006) Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J Immunol 177: 739–747.

30. LanP, ZhangC, HanQ, ZhangJ, TianZ (2013) Therapeutic recovery of hepatitis B virus (HBV)-induced hepatocyte-intrinsic immune defect reverses systemic adaptive immune tolerance. Hepatology 58: 73–85.

31. KennedyPT, SandalovaE, JoJ, GillU, Ushiro-LumbI, et al. (2012) Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B. Gastroenterology 143: 637–645.

32. MiccoL, PeppaD, LoggiE, SchurichA, JeffersonL, et al. (2013) Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B. J Hepatol 58: 225–233.

33. JiC, SastryKS, TiefenthalerG, CanoJ, TangT, et al. (2012) Targeted delivery of interferon-alpha to hepatitis B virus-infected cells using T-cell receptor-like antibodies. Hepatology 56: 2027–2038.

34. LanfordRE, GuerraB, ChavezD, GiavedoniL, HodaraVL, et al. (2013) GS-9620, an oral agonist of Toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees. Gastroenterology 144: 1508–1517.

35. SchurichA, PallettLJ, LubowieckiM, SinghHD, GillUS, et al. (2013) The third signal cytokine IL-12 rescues the anti-viral function of exhausted HBV-specific CD8 T cells. PLoS Pathog 9: e1003208 doi:10.1371/journal.ppat.1003208

36. PeppaD, GillUS, ReynoldsG, EasomNJ, PallettLJ, et al. (2013) Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion. J Exp Med 210: 99–114.

37. SitiaG, AiolfiR, Di LuciaP, MainettiM, FiocchiA, et al. (2012) Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B. Proc Natl Acad Sci U S A 109: E2165–2172.

38. ShouvalD (2013) Focus: quantitative HBsAg measurement as a new surrogate marker for assessment of hepatic fibrosis in HBeAg+ chronic hepatitis B. J Hepatol 58: 1063–1064.