Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection

Oberhardt, Valerie; Hofmann, Maike; Thimme, Robert

doi:10.3390/v14020198

Cited by 11 publications

(10 citation statements)

References 188 publications

(261 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This can hamper HDV clearance and in turn contributing to the persistence of HDV‐infection 34 . In particular, a previous study has revealed the presence of immune‐escape mutations in 6 out of the 11 (54%) analysed CD8+ T‐cell epitopes 34 . Notably, another study has identified the mutation S170N, located in an HLA‐B*15:01‐restricted CD8+ T‐cell epitope, conferring an immune‐evasion phenotype in all patients with this specific HLA 34 …”

Section: Mechanisms Underlying Hdv Persistencementioning

confidence: 99%

“…(Figure 1). This can hamper HDV clearance and in turn contributing to the persistence of HDV‐infection 34 . In particular, a previous study has revealed the presence of immune‐escape mutations in 6 out of the 11 (54%) analysed CD8+ T‐cell epitopes 34 .…”

Section: Mechanisms Underlying Hdv Persistencementioning

confidence: 99%

“…HDV undergoes a constant process of genetic adaptation to the human host that gives rise to a pool of closely related quasispecies that can favour HDV evasion from the cytotoxic immune response. 14,34 (Figure 1). This can hamper HDV clearance and in turn contributing to the persistence of HDV-infection.…”

Section: Immune Escape Mutationsmentioning

confidence: 99%

See 2 more Smart Citations

Novel concepts on mechanisms underlying Hepatitis Delta virus persistence and related pathogenesis

Salpini

D’Anna

Piermatteo

et al. 2022

Journal of Viral Hepatitis

View full text Add to dashboard Cite

Hepatitis Delta virus is the smallest known human virus, exploiting the HBV surface proteins (HBsAg) for the release of its progeny and de novo entry into hepatocytes. Ever growing evidence have highlighted the existence of multiple mechanisms underlying HDV persistence including integrated HBV‐DNA as a source of HBsAg production and the capability of the HDV genome to propagate through cell proliferation, thus supporting a potential HDV persistence even in the absence of HBV. Chronic HDV‐infection causes the most severe form of viral hepatitis, leading to the development of cirrhosis in 15% of cases within 1–2 years and in 50%–60% of cases within 5–10 years. The rates of hepatocellular carcinoma and hepatic decompensation are also 2–3‐fold higher than for HBV mono‐infection. There is the evidence that persistent viral replication plays a key role in triggering liver injury, suggesting the existence of direct viral cytopathic properties that can modulate, synergistically with immune‐responses, the progression towards end‐stage liver diseases. All these aspects can be further exacerbated by the extraordinary degree of viral genetic variability that can promote HDV evasion from immune responses and has enabled viral differentiation into genotypes and subgenotypes with potential different pathobiological properties. In this light, this review aims at providing comprehensive insights of mechanisms (with a focus on virological factors) underlying HDV persistence and pathogenesis, critical in shaping the clinical outcome of the infection. Dissecting these mechanisms is pivotal to optimize therapeutic strategies aimed at fully counteracting this fascinating and fearsome virus.

show abstract

Section: Mechanisms Underlying Hdv Persistencementioning

confidence: 99%

Section: Mechanisms Underlying Hdv Persistencementioning

confidence: 99%

See 1 more Smart Citation

Novel concepts on mechanisms underlying Hepatitis Delta virus persistence and related pathogenesis

Salpini

D’Anna

Piermatteo

et al. 2022

Journal of Viral Hepatitis

View full text Add to dashboard Cite

show abstract

“…Additionally, a portion of HBV patients are co-infected with hepatitis D virus (HDV), which often indicates a poor prognosis. As the smallest known human virus, HDV has perfectly adapted to escape recognition by CD8 + T cells restricted by common human leukocyte antigen (HLA) class I alleles ( 120 ). A recent study suggested that antigen-nonspecific activation of hepatic CD8 + T RM cells may be involved in intrahepatic inflammation and disease progression in HDV infection ( 121 ).…”

Section: Liver T Rm Cells In the Chronic Liver Dis...mentioning

confidence: 99%

Tissue-resident memory T cells in chronic liver diseases: Phenotype, development and function

You

2022

Front. Immunol.

View full text Add to dashboard Cite

Tissue-resident memory (TRM) T cells are a unique subset of memory T cells that are critical for the first line of defense against pathogens or antigens in peripheral non-lymphoid tissues such as liver, gut, and skin. Generally, TRM cells are well adapted to the local environment in a tissue-specific manner and typically do not circulate but persist in tissues, distinguishing them from other memory T cell lineages. There is strong evidence that liver TRM cells provide a robust adaptive immune response to potential threats. Indeed, the potent effector function of hepatic TRM cells makes it essential for chronic liver diseases, including viral and parasite infection, autoimmune liver diseases (AILD), nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC) and liver transplantation. Manipulation of hepatic TRM cells might provide novel promising strategies for precision immunotherapy of chronic liver diseases. Here, we provide insights into the phenotype of hepatic TRM cells through surface markers, transcriptional profiles and effector functions, discuss the development of hepatic TRM cells in terms of cellular origin and factors affecting their development, analyze the role of hepatic TRM cells in chronic liver diseases, as well as share our perspectives on the current status of hepatic TRM cell research.

show abstract

“…Notably, the mechanisms driving the sequence variation of HDV have so far not been studied in detail. In recent studies, it has been shown also for HDV that CD8 + T cells contribute to sequence variation by selecting mutations in targeted epitopes ( 15 , 16 ). HLA class I-associated selection pressure on HDV was also documented at the population level ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Sequence diversity of hepatitis D virus in Mongolia

et al. 2023

View full text Add to dashboard Cite

IntroductionThe Hepatitis Delta Virus (HDV) is a defective, single-stranded RNA virusoid encoding for a single protein, the Hepatitis Delta Antigen (HDAg), which requires the hepatitis B virus (HBV) envelope protein (HBsAg) for its transmission. Currently, hepatitis D is the most aggressive form of viral hepatitis and treatment options are limited. Worldwide 12 million people are chronically infected with HDV being at high risk for progression to cirrhosis and development of liver cancer.ObjectivesAlthough it is well established that Mongolia is the country with the highest prevalence of HDV infections, the information on the molecular epidemiology and factors contributing to HDV sequence diversity are largely unclear. The aim of the study was to characterize the sequence diversity of HDV in rural areas from Mongolia and to determine the extent of HLA class I-associated selection pressure.Patients and methodsFrom the HepMongolia cohort from rural areas in Mongolia, 451 HBsAg-positive individuals were selected and anti-HDV, HDV-RNA and the sequence of the large HDAg was determined. For all individuals the HLA class I locus was genotyped. Residues under selection pressure in the presence of individual HLA class I types were identified with the recently published analysis tool HAMdetector.ResultsOf 431 HBsAg positive patients, 281 were anti-HDV positive (65%), and HDV-RNA could be detected in 207 of 281 (74%) of patients. The complete large HDAg was successfully sequenced from 131 samples. Phylogenetic analysis revealed that all Mongolian HDV isolates belong to genotype 1, however, they separate into several different clusters without clear regional association. In turn, from phylogeny there is strong evidence for recent local transmission events. Importantly, we found multiple residues with strong support for HLA class I-associated selection pressure consistent with a functional CD8+ T cell response directed against HDV.ConclusionHDV isolates from Mongolia are highly diverse. The molecular epidemiology suggests circulation of multiple subtypes and provides evidence for ongoing recent transmissions.

show abstract

Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection

Cited by 11 publications

References 188 publications

Novel concepts on mechanisms underlying Hepatitis Delta virus persistence and related pathogenesis

Novel concepts on mechanisms underlying Hepatitis Delta virus persistence and related pathogenesis

Tissue-resident memory T cells in chronic liver diseases: Phenotype, development and function

Sequence diversity of hepatitis D virus in Mongolia

Contact Info

Product

Resources

About