Interaction Between Hepatitis B Virus and Toll-Like Receptors: Current Status and Potential Therapeutic Use for Chronic Hepatitis B

Overview

Journal Vaccines (Basel)

Date 2018 Jan 17

PMID 29337856

Citations 39

Authors

Zhiyong Ma

Qian Cao

Yong Xiong

Ejuan Zhang

Mengji Lu

Affiliations

Soon will be listed here.

Abstract

Immune defense against infection with the hepatitis B virus (HBV) is complex and involves both host innate and adaptive immune systems. It is well accepted that the development of sufficient HBV-specific T cell and B cell responses are required for controlling an HBV infection. However, the contribution of innate immunity to removing HBV has been explored in recent years. Toll-like receptors (TLRs) are recognized as the first line of antiviral immunity because they initiate intracellular signaling pathways to induce antiviral mediators such as interferons (IFNs) and other cytokines. Recent studies show that the activation of TLR-mediated signaling pathways results in a suppression of HBV replication in vitro and in vivo. However, HBV has also evolved strategies to counter TLR responses including the suppression of TLR expression and the blockage of downstream signaling pathways. Antiviral treatment in chronic HBV-infected patients leads to an upregulation of TLR expression and the restoration of its innate antiviral functions. Thus, TLR activation may serve as an additional immunotherapeutic option for treating chronic HBV infection in combination with antiviral treatment.

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References

Niu C, Li L, Daffis S, Lucifora J, Bonnin M, Maadadi S . Toll-like receptor 7 agonist GS-9620 induces prolonged inhibition of HBV via a type I interferon-dependent mechanism. J Hepatol. 2017; 68(5):922-931. DOI: 10.1016/j.jhep.2017.12.007. View

Roggendorf M, Kosinska A, Liu J, Lu M . The Woodchuck, a Nonprimate Model for Immunopathogenesis and Therapeutic Immunomodulation in Chronic Hepatitis B Virus Infection. Cold Spring Harb Perspect Med. 2015; 5(12). PMC: 4665037. DOI: 10.1101/cshperspect.a021451. View

Wu J, Huang S, Zhao X, Chen M, Lin Y, Xia Y . Poly(I:C) treatment leads to interferon-dependent clearance of hepatitis B virus in a hydrodynamic injection mouse model. J Virol. 2014; 88(18):10421-31. PMC: 4178898. DOI: 10.1128/JVI.00996-14. View

Liu J, Zhang E, Ma Z, Wu W, Kosinska A, Zhang X . Enhancing virus-specific immunity in vivo by combining therapeutic vaccination and PD-L1 blockade in chronic hepadnaviral infection. PLoS Pathog. 2014; 10(1):e1003856. PMC: 3879364. DOI: 10.1371/journal.ppat.1003856. View

Luangsay S, Gruffaz M, Isorce N, Testoni B, Michelet M, Faure-Dupuy S . Early inhibition of hepatocyte innate responses by hepatitis B virus. J Hepatol. 2015; 63(6):1314-22. DOI: 10.1016/j.jhep.2015.07.014. View

Cooper C, Mackie D . Hepatitis B surface antigen-1018 ISS adjuvant-containing vaccine: a review of HEPLISAV™ safety and efficacy. Expert Rev Vaccines. 2011; 10(4):417-27. DOI: 10.1586/erv.10.162. View

Huang Y, Lin S, Wei S, Hu J, Chang H, Huang S . Reduced Toll-like receptor 3 expression in chronic hepatitis B patients and its restoration by interferon therapy. Antivir Ther. 2013; 18(7):877-84. DOI: 10.3851/IMP2630. View

Xie Q, Shen H, Jia N, Wang H, Lin L, An B . Patients with chronic hepatitis B infection display deficiency of plasmacytoid dendritic cells with reduced expression of TLR9. Microbes Infect. 2009; 11(4):515-23. DOI: 10.1016/j.micinf.2009.02.008. View

Deng G, Ge J, Liu C, Pang J, Huang Z, Peng J . Impaired expression and function of TLR8 in chronic HBV infection and its association with treatment responses during peg-IFN-α-2a antiviral therapy. Clin Res Hepatol Gastroenterol. 2017; 41(4):386-398. DOI: 10.1016/j.clinre.2016.12.006. View

10.

Cottalorda A, Verschelde C, Marcais A, Tomkowiak M, Musette P, Uematsu S . TLR2 engagement on CD8 T cells lowers the threshold for optimal antigen-induced T cell activation. Eur J Immunol. 2006; 36(7):1684-93. DOI: 10.1002/eji.200636181. View

11.

Fisicaro P, Valdatta C, Boni C, Massari M, Mori C, Zerbini A . Early kinetics of innate and adaptive immune responses during hepatitis B virus infection. Gut. 2009; 58(7):974-82. DOI: 10.1136/gut.2008.163600. View

12.

Ijichi K, Mitamura K, Ida S, Machida H, Shimada K . In vivo antiviral effects of mismatched double-stranded RNA on duck hepatitis B virus. J Med Virol. 1994; 43(2):161-5. DOI: 10.1002/jmv.1890430212. View

13.

Niu J, Wang Y, Dixon R, Bowden S, Qiao M, Einck L . The use of ampligen alone and in combination with ganciclovir and coumermycin A1 for the treatment of ducks congenitally-infected with duck hepatitis B virus. Antiviral Res. 1993; 21(2):155-71. DOI: 10.1016/0166-3542(93)90051-j. View

14.

Yu S, Chen J, Wu M, Chen H, Kato N, Yuan Z . Hepatitis B virus polymerase inhibits RIG-I- and Toll-like receptor 3-mediated beta interferon induction in human hepatocytes through interference with interferon regulatory factor 3 activation and dampening of the interaction between.... J Gen Virol. 2010; 91(Pt 8):2080-2090. DOI: 10.1099/vir.0.020552-0. View

15.

Vanlandschoot P, Van Houtte F, Ulrichts P, Tavernier J, Leroux-Roels G . Immunostimulatory potential of hepatitis B nucleocapsid preparations: lipopolysaccharide contamination should not be overlooked. J Gen Virol. 2005; 86(Pt 2):323-331. DOI: 10.1099/vir.0.80605-0. View

16.

Webster G, Reignat S, Maini M, Whalley S, Ogg G, King A . Incubation phase of acute hepatitis B in man: dynamic of cellular immune mechanisms. Hepatology. 2000; 32(5):1117-24. DOI: 10.1053/jhep.2000.19324. View

17.

Xu Y, Hu Y, Shi B, Zhang X, Wang J, Zhang Z . HBsAg inhibits TLR9-mediated activation and IFN-alpha production in plasmacytoid dendritic cells. Mol Immunol. 2009; 46(13):2640-6. DOI: 10.1016/j.molimm.2009.04.031. View

18.

Reynolds J, Dong C . Toll-like receptor regulation of effector T lymphocyte function. Trends Immunol. 2013; 34(10):511-9. DOI: 10.1016/j.it.2013.06.003. View

19.

Bleau C, Filliol A, Samson M, Lamontagne L . Mouse Hepatitis Virus Infection Induces a Toll-Like Receptor 2-Dependent Activation of Inflammatory Functions in Liver Sinusoidal Endothelial Cells during Acute Hepatitis. J Virol. 2016; 90(20):9096-113. PMC: 5044860. DOI: 10.1128/JVI.01069-16. View

20.

Cooper C, Davis H, Angel J, Morris M, Elfer S, Seguin I . CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults. AIDS. 2005; 19(14):1473-9. DOI: 10.1097/01.aids.0000183514.37513.d2. View