Effect of telbivudine therapy on the cellular immune response in chronic hepatitis B

Chen, Yu; Li, Xuefen; Ye, Bo; Yang, Xianzhi; Wu, Wei; Zheng, Min; Pan, Xiaoping; Cao, Hong; Li, Lanjuan

doi:10.1016/j.antiviral.2011.04.008

Cited by 53 publications

(48 citation statements)

References 31 publications

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“…In this study, the results demonstrated a negative correlation between HBV-DNA levels and HBV-specific CTL responses in untreated CHB patients. These findings are in agreement with previous studies (14,17) and strengthen the evidence for an independent effect of viral load on the cellular immune response. …”

Section: Discussionsupporting

confidence: 93%

“…A proportion of the untreated patients exhibited HBV-specific CTL responses that were weak. These findings are consistent with the majority of previous studies (7,10,14). In the treated CHB patients, the frequency and magnitude of the antigen-specific T cell responses were significantly higher than those in the untreated CHB patient group.…”

Section: Discussionsupporting

confidence: 92%

“…The mechanisms that may contribute to complete eradication of HBV infection include the innate immune responses and the acquired CD4 + and CD8 + T-cell responses, particularly the HBV-specific T-cell responses (8). These mechanisms have been shown to be of paramount importance in evaluating the future direction of antiviral treatment for HBV-infected patients (12)(13)(14). It may be beneficial to identify any immune function alterations in the patients with persistent suppression of HBV replication following antiviral therapy that may aid in predicting the long-term efficacy of antiviral therapy and provide immunotherapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

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Effects of antiviral therapy on the cellular immune response in patients with chronic hepatitis B

Luo

Xia

Huang

et al. 2014

Molecular Medicine Reports

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Abstract.A weak T-cell immune response to the hepatitis B virus (HBV) is hypothesized to be the primary cause of chronic HBV infection. Emerging evidence suggests that long-term effective antiviral therapy restores the HBV-specific T-cell response from exhaustion. However, the extent to which the cellular immune response can be restored following the persistent suppression of HBV replication by antiviral therapy remains unclear. In order to investigate this question, 46 patients with chronic hepatitis B (CHB) treated with nucleos(t) ide analogues who demonstrated persistent suppression of HBV replication [defined as undetectable HBV DNA, hepatitis B e antigen (HBeAg) negative and adherence to antiviral therapy], 22 untreated CHB patients, 15 patients with acute hepatitis B (AHB) and 10 healthy adults were recruited. HBV-specific interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) assay and HBV-specific T-cell proliferation analysis were performed with a panel of overlapping peptides covering the envelope and core antigens. Data from this study showed that the HBV-specific immune responses to the peptide pools of the envelope and core protein in the treated patients were stronger than those in the untreated CHB patients, but significantly weaker than those in the AHB patients and healthy adults. A higher frequency of response to S than C peptide pools was confirmed by the IFN-γ ELISPOT assay in the treated CHB patients. The restoration of antiviral immunity was clearly associated with a reduction in HBV DNA and the duration of HBV DNA suppression. In conclusion, the HBV-specific immune responses in the CHB patients can be significantly restored from exhaustion following the persistent suppression of HBV replication as a result of antiviral treatment with nucleos(t)ide analogues.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Effects of antiviral therapy on the cellular immune response in patients with chronic hepatitis B

Luo

Xia

Huang

et al. 2014

Molecular Medicine Reports

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“…Serum HBV DNA was quantitatively detected using real-time polymerase chain reaction (PCR) with commercial kits as described previously. 12 The minimal detection standard for PCR contained 500 copies/ ml. HBV genotypes were determined with sequence detection via PCR.…”

Section: Biochemical Serological and Virological Assaysmentioning

confidence: 99%

“…All products were directly sequenced with an HBV Genotype Real Time PCR Kit (ZJ Bio-Tech, Shanghai, China) and run on MegaBACE 500 according to the manufacturer's instructions, as has been previously described in detail. 12 PBMC separation and T-cell subset sorting PBMCs were prepared from whole blood treated with 10 ml of fresh EDTA-K 2 anticoagulate by a Ficoll-Paque density gradient separation (CEDARLANE, Burlington, CANADA). Because we could not recover enough PBMCs useful for sorting T cells into subsets, PBMC samples were taken from 30 of 38 recovered AHI subjects and 25 of 27 healthy controls for further sorting.…”

Section: Biochemical Serological and Virological Assaysmentioning

confidence: 99%

Profiling the repertoire of T-cell receptor beta-chain variable genes in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection

Yang

Chen

et al. 2014

Cell Mol Immunol

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The profile of T-cell receptor beta-chain variable (TRBV) genes usually skews in subjects with virus infection or cancer. The gene melting spectral pattern (GMSP) can be used to determine the profile of the TRBV gene family. To explore the portrait of the TRBV family in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection (AHI), peripheral blood mononuclear cells (PBMCs) were separated and further sorted into CD41 and CD8 1T-cell subsets. The molecular features of the TRBV complementary determining region 3 (CDR3) motifs were determined using GMSP analysis. When a GMSP profile showed a single peak, the monoclonally expanded TRBV gene was cloned and sequenced. Skewed expansions of multiple TRBV genes were observed among the CD4 1 and CD8 1 T-cell subsets and the PBMCs. The frequency of monoclonally expanded TRBV genes in the CD8 1 T-cell subset was significantly higher than that of the CD4 1 T-cell subset and the PBMCs. Compared to other members of the TRBV gene family, TRBV11, BV15 and BV20 were predominantly expressed in the repertoire of peripheral blood lymphocytes in recovered AHI subjects. The relatively conserved amino acid motifs of TRBV5.1 and BV20 CDR3 were also detected in the CD4 1 and CD8 1 T-cell subsets. These results demonstrate the presence of multiple biased TRBV families in recovered AHI subjects. TRBV11, BV15 and BV20, especially from the CD8 1 T-cell subset, may be relevant to the pathogenesis of subjects with AHI. The preferentially selected TRBV5.1 and BV20 with the relatively conserved CDR3 motif may be potential targets for personalized treatments of chronic HBV infection.

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Anti‐DNA Virus Agents

Herdewijn¹,

Gu²,

Clercq³

2021

Burger's Medicinal Chemistry and Drug Discovery

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Although most of the drugs that are used to treat deoxyribonucleic acid (DNA) virus infections have been on the market for more than 10 years, anti‐DNA virus drug discovery remains an active field of research. There are still DNA viruses that are important human pathogens for which no therapy is available (i.e. adenovirus), for which the available drugs show considerable toxicity (i.e. cytomegalovirus), or for which the current drug therapy is insufficient to eradicate the virus (i.e. hepatitis B virus). In this article, we have provided an overview of the anti‐DNA virus drugs that are presently on the market together with a description of the new compounds, all active against DNA viruses, covering the literature of the past 10 years. We have focused on the structure of newly discovered compounds, and the mechanism of action and clinical data, when available. Although the major efforts are still in the nucleotide antimetabolite field, the anti‐DNA virus field of research and development has shifted recently in the direction of the study of more common heterocyclic structures as protein inhibitors.

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Effect of telbivudine therapy on the cellular immune response in chronic hepatitis B

Cited by 53 publications

References 31 publications

Effects of antiviral therapy on the cellular immune response in patients with chronic hepatitis B

Effects of antiviral therapy on the cellular immune response in patients with chronic hepatitis B

Profiling the repertoire of T-cell receptor beta-chain variable genes in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection

Anti‐DNA Virus Agents

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