Mechanisms of HBV immune evasion

Kuipery, Adrian; Gehring, Adam J.; Isogawa, Masanori

doi:10.1016/j.antiviral.2020.104816

Cited by 48 publications

(44 citation statements)

References 144 publications

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“…The responses might be similar to those in patients with acute self-limiting HBV infection. In such patients, robust, polyclonal, and multi-specific CD4 and CD8 T-cell responses and neutralizing antibody responses were observed [12]. Actually, the levels of IgM-HBc were high in cases 1 and 2, similar to acute infection with HBV.…”

Section: Discussionmentioning

confidence: 95%

“…Actually, the levels of IgM-HBc were high in cases 1 and 2, similar to acute infection with HBV. In contrast, adaptive immune responses in chronically HBV-infected patients are known to be depleted qualitatively and/or quantitatively [12], which is characterized by the impairment of effector cytotoxic activity and cytokine production. Also, the expression of inhibitory receptors, such as programmed cell death-1 and cytotoxic T lymphocyte-associated antigen-4, is increased on the surface of exhausted T cells [13].…”

Section: Discussionmentioning

confidence: 99%

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Hepatitis B Virus Reactivation with Discontinuation of Nucleoside Analogue in Patients Who Received Allogeneic Hematopoietic Stem Cell Transplantation

Tsuruoka

Inoue

Onishi

et al. 2021

Case Rep Gastroenterol

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Reactivation of hepatitis B virus (HBV) is known to occur frequently after hematopoietic stem cell transplantation (HSCT). The reactivation can be prevented by nucleos(t)ide analogue (NA), but it is unclear how long NA should be continued. Here, we report 3 cases of HBV reactivation with discontinuation of NA following the discontinuation of immunosuppressive therapies after HSCT. Three male patients aged 34, 59, and 54 years received allogeneic HSCT (allo-HSCT) for chronic myeloid leukemia, mixed phenotype acute leukemia, and myelodysplastic syndrome, respectively. Before HSCT, 2 patients were positive for hepatitis B surface antigen (HBsAg) and 1 patient was negative for HBsAg and positive for antibodies to hepatitis B core antigen. NA (lamivudine or entecavir) was started at the same time as HSCT and stopped after the discontinuation of immunosuppressive therapies. In all patients, the serum HBV DNA levels were increased after the discontinuation of NAs. Two of the three patients developed severe hepatitis with high levels of HBV DNA (7.5 and 7.4 log IU/mL, respectively). A patient without hepatitis was re-administered NA soon after the HBV DNA started to increase (3.3 log IU/mL). Interestingly, the 2 patients who developed hepatitis cleared HBsAg promptly after the recovery from hepatitis and they could stop NAs without the reversion of HBsAg. It was speculated that transplanted immune cells, which were naïve for HBV, react strongly with HBV antigens that were increased after the NA discontinuation. The discontinuation of NA after allo-HSCT is not recommended generally because strong hepatitis might be induced even after several years.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus Reactivation with Discontinuation of Nucleoside Analogue in Patients Who Received Allogeneic Hematopoietic Stem Cell Transplantation

Tsuruoka

Inoue

Onishi

et al. 2021

Case Rep Gastroenterol

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“…These include empty envelopes of HBsAg (subviral particles), virions containing RNA, or a defective DNA genome, as well as naked nucleocapsids (lacking envelope) ( Figure 1 ) [ 63 ]. These defective particles do not participate in viral replication, although the subviral HBsAg particles help suppress antiviral immunity [ 18 ].…”

Section: Hbv Replication Cyclementioning

confidence: 99%

Recent Advances in Hepatitis B Treatment

et al. 2021

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Hepatitis B virus infection affects over 250 million chronic carriers, causing more than 800,000 deaths annually, although a safe and effective vaccine is available. Currently used antiviral agents, pegylated interferon and nucleos(t)ide analogues, have major drawbacks and fail to completely eradicate the virus from infected cells. Thus, achieving a “functional cure” of the infection remains a real challenge. Recent findings concerning the viral replication cycle have led to development of novel therapeutic approaches including viral entry inhibitors, epigenetic control of cccDNA, immune modulators, RNA interference techniques, ribonuclease H inhibitors, and capsid assembly modulators. Promising preclinical results have been obtained, and the leading molecules under development have entered clinical evaluation. This review summarizes the key steps of the HBV life cycle, examines the currently approved anti-HBV drugs, and analyzes novel HBV treatment regimens.

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“…Similarly, HBV-mediated inhibition of innate signaling pathways within infected hepatocytes has been reported but remains controversial. Both topics were recently reviewed with indepth coverage of the complexity of the data [11,12]. However, observations have been made in patients demonstrating that alterations in innate immunity occur, either impacting the expression of Toll-like receptors or modulating immune cell composition in the peripheral blood [13].…”

Section: Introductionmentioning

confidence: 99%

RNA Interference Therapy for Chronic Hepatitis B Predicts the Importance of Addressing Viral Integration When Developing Novel Cure Strategies

Wooddell

Gehring

Yuen

et al. 2021

Viruses

Self Cite

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Chronic hepatitis B infection remains a globally important cause of morbidity and mortality and has recently undergone a renaissance in therapeutic interest with increased pre-clinical and clinical testing of new drug classes. One of the first new classes in the clinic was RNA interference agents, which have the potential to impact the entire viral life cycle by reducing all virus-produced mRNA. Early clinical testing with the first of these agents in the clinic, ARC-520, demonstrated that rapid and deep reductions in viral proteins, RNA and DNA could be produced with this approach, but also the surprising insight that HBsAg production from incomplete HBV DNA integrated into the host genome appears to play a heretofore unappreciated and important role in maintaining circulating HBsAg, thought to play a fundamental role in preventing host clearance of the virus. Thus, accounting for viral DNA integration in novel HBV treatment approaches may prove to be essential to achieving successful finite therapies of this difficult to treat chronic infection.

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Mechanisms of HBV immune evasion

Cited by 48 publications

References 144 publications

Hepatitis B Virus Reactivation with Discontinuation of Nucleoside Analogue in Patients Who Received Allogeneic Hematopoietic Stem Cell Transplantation

Hepatitis B Virus Reactivation with Discontinuation of Nucleoside Analogue in Patients Who Received Allogeneic Hematopoietic Stem Cell Transplantation

Recent Advances in Hepatitis B Treatment

RNA Interference Therapy for Chronic Hepatitis B Predicts the Importance of Addressing Viral Integration When Developing Novel Cure Strategies

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