Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population

Fischer, Janett; Koukoulioti, Eleni; Schott, Eckart; Fülöp, B; Heyne, R.; Berg, Thomas

doi:10.1038/s41598-018-31065-6

Cited by 23 publications

(18 citation statements)

References 41 publications

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“…Several studies have found that genetic variants on the human leucocyte antigen (HLA)-DP gene are associated with HBsAg-seroclearance during the natural history of infection [ 64 ] or during treatment with NA [ 65 ], which seems to be consistent across different populations [ 66 ]. Other polymorphisms on genes linked to immunological function, such as the toll-like receptor 3 [ 67 ], interleukin 10 [ 68 ], and T-cell immunoglobulin and mucin domain-containing molecule 3 genes [ 69 ], have also shown to be linked to the natural progression of HBV infection and are less consistently studied [ 66 ]. There have been very few studies examining the role of genetic polymorphisms on HBsAg-seroclearance in HIV-HBV co-infected individuals, apart from the IL28B haplotype showing no association [ 70 ].…”

Section: Determinants Of Functional Cure During Treated Hiv-hbv Co-infectionmentioning

confidence: 99%

Functional Cure of Hepatitis B Virus Infection in Individuals With HIV-Coinfection: A Literature Review

Boyd

Dezanet

Lacombe

2021

Viruses

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In individuals infected with hepatitis B virus (HBV), the loss of hepatitis B surface antigen (HBsAg) is the ultimate therapeutic goal, which defines “functional cure.” For individuals living with human immunodeficiency virus (HIV), functional cure occurs roughly 2 per 100 person-years during potent anti-HBV containing antiretroviral therapy. Although this rate may be higher than expected in treated HBV mono-infected individuals, rates of functional cure widely vary between studies (0.6–10.5 per 100 person-years). Similar to HBV mono-infection, the phase of HBV infection, HBV (sub-)genotypes and hepatitis B “e” Ag-negative variants are associated with functional cure in treated HIV-HBV co-infection. In specifically HIV-HBV co-infected individuals, strong increases in CD4+ T cell counts after treatment initiation have also been linked to functional cure, yet this finding is inconsistent across studies. Several markers directly or indirectly reflecting HBV activity are being developed to predict functional cure, such as quantification of HBsAg, hepatitis B core-related antigen, HBsAg protein composition, anti-hepatitis B core antibodies and interferon-gamma-inducible protein 10. Few have been assessed during treatment in HIV-HBV co-infected individuals and none have been validated to predict functional cure. Novel therapeutics for HBV cure are essential for individuals with HIV-HBV co-infection and need to be separately evaluated in this population.

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Section: Determinants Of Functional Cure During Treated Hiv-hbv Co-infectionmentioning

confidence: 99%

Functional Cure of Hepatitis B Virus Infection in Individuals With HIV-Coinfection: A Literature Review

Boyd

Dezanet

Lacombe

2021

Viruses

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“…TLR3 is activated at the transcriptional level by interferon regulatory factors 3 and 7 (IRF3, IRF7). IFN-β expression also regulates initiate antiviral immunity, but can cause liver damage and necrosis [47].…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology-based study on the mechanism of Yiganling capsule in hepatitis B treatment

Lü

Zhou

et al. 2020

BMC Complement Med Ther

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Background: Yiganling (YGL) capsule is a traditional Chinese medicine preparation consisting of eight herbs that has been clinically proven to have a favorable treatment effect on Hepatitis B (HB). However, due to its multiple targets and multi-pharmacological effects, the mechanisms of YGL capsule in the treatment of HB are unknown. Methods: First, the chemical constituents of YGL capsules were obtained from the Chinese medicine database, and YGL capsules were constructed. Second, active compounds were screened by the ADME model. The target fishing model was used to screen the corresponding targets of active compounds and to construct a compounds and compound targets network. Using human disease databases and literature mining, we systematically identified genes associated with HB, constructed disease-specific protein-protein interaction networks, and performed clustering and enrichment analyses of these networks. These networks were then merged to obtain a compounddisease target network, and cluster and enrichment analyses were performed on the compound-disease target network to acquire a compounds-disease targets-mechanism network and a clustering network. Results: We successfully built eight pharmacological network diagrams, including four primary networks and other network maps. The four dominating network maps included a HB disease-associated protein-protein interaction network, a YGL capsule compounds-target network, a YGL capsule ingredient target-HB disease target network, and a YGL-HB disease mechanism network. Other networks included a pathway of HB disease targets, the HB disease protein-protein interaction cluster analysis network, and the YGL-HB target clustering network. Conclusion: This study successfully forecasted, illuminated, and confirmed the synergistic effects of HB disease molecules and discovered the potential of HB relevant targets, clusters, and target-related biological processes and signaling pathways. Our research not only provides theoretical support for the molecular and pharmacological mechanisms of YGL capsule in HB treatment, but also provides new research methods for the study of the other traditional Chinese medicinal compounds.

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“…Activation of mDC using TLR3 ligands leads to improved NK cell function in CHB infection (Tjwa et al, 2012). Deterioration: TLR3 polymorphism rs3775291 was associated with an increased risk of developing CHB (Geng et al, 2016;Fischer et al, 2018). Protection: TLR3 restricts WNV replication in neurons and antagonizes against NS1 (Daffis et al, 2008;Wilson et al, 2008).…”

Section: Antiviral Effects Of Tlr3mentioning

confidence: 99%

“…Wang K et al (2010) found that messenger RNA (mRNA) levels of TLR3 increased in CHB in the active phase, suggesting that TLR3 may play a vital role in starting innate immunity. Nevertheless, recent reports showed that the TLR3 polymorphism rs3775291 was associated with reduced spontaneous hepatitis B surface antigen (HBsAg) seroclearance (SC) of HBV infection and an increased risk of developing CHB (Geng et al, 2016;Fischer et al, 2018).…”

Section: Antiviral Effects Of Tlr3mentioning

confidence: 99%

Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses

Chen

Lin

Zhao

et al. 2021

J. Zhejiang Univ. Sci. B

111

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Toll-like receptor 3 (TLR3) is a member of the TLR family, mediating the transcriptional induction of type I interferons (IFNs) proinflammatory cytokines, and chemokines, thereby collectively establishing an antiviral host response. Studies have shown that unlike other TLR family members, TLR3 is the only RNA sensor that is utterly dependent on the Toll-interleukin-1 receptor (TIR)-domain-containing adaptor-inducing IFN-β (TRIF). However, the details of how the TLR3-TRIF signaling pathway works in an antiviral response and how it is regulated are unclear. In this review we focus on recent advances in understanding the antiviral mechanism of the TRIF pathway and describe the essential characteristics of TLR3 and its antiviral effects. Advancing our understanding of TLR3 may contribute to disease diagnosis and could foster the development of novel treatments for viral diseases.

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Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population

Cited by 23 publications

References 41 publications

Functional Cure of Hepatitis B Virus Infection in Individuals With HIV-Coinfection: A Literature Review

Functional Cure of Hepatitis B Virus Infection in Individuals With HIV-Coinfection: A Literature Review

Network pharmacology-based study on the mechanism of Yiganling capsule in hepatitis B treatment

Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses

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