Hepatitis Delta Virus (HDV) and Delta-Like Agents: Insights Into Their Origin

Hepatitis delta virus (HDV) is a human pathogen, and the only known species in the genus Deltavirus. HDV is a satellite virus and depends on the hepatitis B virus (HBV) for packaging, release, and transmission. Extracellular HDV virions contain the genomic HDV RNA, a single-stranded negative-sense and covalently closed circular RNA molecule, which is associated with the HDV-encoded delta antigen forming a ribonucleoprotein complex, and enveloped by the HBV surface antigens. Replication occurs in the nucleus and is mediated by host enzymes and assisted by cis-acting ribozymes allowing the formation of monomer length molecules which are ligated by host ligases to form unbranched rod-like circles. Recently, meta-transcriptomic studies investigating various vertebrate and invertebrate samples identified RNA species with similarities to HDV RNA. The delta-like agents may be representatives of novel subviral agents or satellite viruses which share with HDV, the self-complementarity of the circular RNA genome, the ability to encode a protein, and the presence of ribozyme sequences. The widespread distribution of delta-like agents across different taxa with considerable phylogenetic distances may be instrumental in comprehending their evolutionary history by elucidating the transition from transcriptome to cellular circular RNAs to infectious subviral agents

Imager - A mobile health mental imagery‐based ecological momentary intervention targeting reward sensitivity: A randomized controlled trial

Robust reward sensitivity may help preserve mental well‐being in the face of adversity and has been proposed as a key stress resilience factor. Here, we present a mobile health application, “Imager,” which targets reward sensitivity by training individuals to create mental images of future rewarding experiences. We conducted a two‐arm randomized controlled trial with 95 participants screened for reward sensitivity. Participants in the intervention group received an ecological momentary intervention—Imager, which encouraged participants to create mental images of rewarding events for 1 week. The control group participants received only ecological momentary assessment, without the instruction to generate mental images. Adherence to Imager was high; participants in the intervention group engaged in 88% of the planned activities. In the follow‐up assessment, the intervention group reported less mental health symptoms, mainly in depression (β = −0.34, df = 93, p = .004) and less perceived stress (β = −0.18, df = 93, p = .035), than control group participants and compared with the baseline assessment. Our results show the positive effects of Imager on mental health symptoms. The encouraging effects of the app on mental health outcomes may lead to greater use of ecological momentary interventions in the clinical preventive practice of affective disorders

Burst versus continuous delivery design in digital mental health interventions: Evidence from a randomized clinical trial

Objective:Digital mental health interventions delivered via smartphone-based apps effectively treat various conditions; however, optimizing their efficacy while minimizing participant burden remains a key challenge. In this study, we investigated the potential benefits of a burst delivery design (i.e. interventions delivered only in pre-defined time intervals) in comparison to the continuous delivery of interventions.Methods:We randomly assigned 93 participants to the continuous delivery (CD) or burst delivery (BD) group. The CD group engaged in ReApp, a mobile app that increases positive cognitive reappraisal with a consistent delivery schedule that provides five prompts per day throughout the 3-week-long study, while the BD group received five daily prompts only in the first and third weeks of the study.Results:No significant differences were found between the groups in terms of adherence, mental health outcomes (specifically depressive and anxiety symptoms), level of perceived stress, and perceived helpfulness of intervention. The BD group showed a significantly decreased perceived difficulty of intervention over time.Conclusions:The results suggest that the burst delivery may be as suitable for digital mental health interventions as the continuous delivery. The perceived difficulty of the intervention declined more steeply for the BD group, indicating that it improved the feasibility of the positive cognitive reappraisal intervention without hurting its efficacy. This outcome may inform the design of less burdensome interventions with improved outcomes in future research

The L80I Substitution in the Reverse Transcriptase Domain of the Hepatitis B Virus Polymerase Is Associated with Lamivudine Resistance and Enhanced Viral Replication In Vitro▿

Long-term lamivudine (LMV) treatment of chronic hepatitis B almost inevitably engenders viral resistance. Mutations that result in the replacement of the methionine at position 204 of the deoxynucleoside triphosphate-binding site of the hepatitis B virus (HBV) reverse transcriptase (rt) by isoleucine, valine, or (rarely) serine (rtM204I/V/S) confer high-level resistance to LMV but reduce replication efficiency. The subsequent selection or coselection of secondary mutations that partially restore replication efficiency is common and may influence drug resistance. Genotyping has shown that LMV treatment can select for HBV rtL80V/I mutants, but their prevalence and phenotype have not been documented. Analysis of a large sequence database revealed that rtL80V/I occurred almost exclusively in association with LMV resistance, and 85% of these isolates encoded rtL80I. Coselection of rtL80V/I occurred in 46% of isolates in which LMV resistance was attributable to rtM204I but only 9% of those in which resistance was attributable to rtM204V. Moreover, rtL80V/I did not occur in HBV genotype A isolates but occurred at similar frequencies in genotype B, C, and D isolates. In vitro phenotyping showed that although the rtL80I mutant by itself replicated less efficiently and was hypersensitive to LMV compared to the replication efficiency and sensitivity of its wild-type parent, the presence of rtL80I enhanced the replication efficiency of rt204I/V mutants without significantly affecting LMV resistance. Molecular modeling revealed that rt80 does not interact directly with the enzyme's substrates. Collectively, these results suggest that coselection of rtL80V/I and rtM204I/V occurs because the former compensates for the loss of replication efficiency associated with the acquisition of LMV resistance, particularly in the case of rtM204I

A Divergent Hepatitis D-Like Agent in Birds

Hepatitis delta virus (HDV) is currently only found in humans and is a satellite virus that depends on hepatitis B virus (HBV) envelope proteins for assembly, release, and entry. Using meta-transcriptomics, we identified the genome of a novel HDV-like agent in ducks. Sequence analysis revealed secondary structures that were shared with HDV, including self-complementarity and ribozyme features. The predicted viral protein shares 32% amino acid similarity to the small delta antigen of HDV and comprises a divergent phylogenetic lineage. The discovery of an avian HDV-like agent has important implications for the understanding of the origins of HDV and sub-viral agents

Imager – An mHealth mental imagery-based ecological momentary intervention targeting reward sensitivity: A randomized controlled trial

Introduction: Robust sensitivity to reward may help preserve positive emotions in the face of adversity and has been proposed as a key resilience factor. We describe the development, feasibility, and efficacy of an mHealth application, Imager, which targets reward sensitivity by training individuals to create mental images of future rewarding experiences. Methods: We conducted a randomized controlled trial with healthy student participants screened for low reward sensitivity. Fifty-one participants in the intervention group (IG) received an ecological momentary intervention (EMI) - Imager, including 10 ecological momentary assessment (EMA) prompts per day over 7 days, of which three were combined with an instruction to engage in a mental imagery training. This part encouraged participants to create a mental image of a rewarding event. Forty-four participants from the control group (CG) received 10 EMA prompts per day, without the option of performing mental imagery training. Results: Adherence to Imager was high; participants in the IG engaged in 88.4% of the planned EMAs and EMIs. Intervention group participants reported fewer mental health symptoms, mainly in depression (=−0.34, df=93, p=0.004) and less perceived stress (=−0.18, df=93, p=0.035) than CG participants. There were no significant changes in self-reported reward sensitivity in the IG. Conclusions: Mental imagery training of future rewarding experiences was accepted by participants and integrated into their everyday lives. Our results show positive effects of Imager on mental well-being, although direct target engagement – self-reported reward sensitivity – was not confirmed. Prospective studies are needed to investigate the psychological, physiological, behavioral and neural mechanisms underlying Imager’s effects based on additional data on other populations

Burst versus continuous delivery design in digital mental health interventions: evidence from a randomized clinical trial.

Objective: Digital mental health interventions delivered via smartphone-based apps effectively treat various conditions, but optimizing their efficacy while minimizing participant burden remains a key challenge. Here, we investigated the potential benefits of a burst delivery design, i.e., intervention delivered only in pre-defined time intervals, in comparison to the continuous delivery of the intervention. Methods: We randomly assigned ninety-three participants to continuous delivery (CD) or burst delivery (BD) groups. The CD engaged in ReApp, a mobile app that increases positive cognitive reappraisal with a consistent delivery schedule with five prompts per day throughout the three-week-long study, while BD received five daily prompts only in the first and third weeks of the study. Results: No significant differences were found between the groups in adherence, mental health outcomes, specifically depressive and anxiety symptoms, and the level of perceived stress, and perceived helpfulness of the intervention. BD group significantly decreased in perceived difficulty of the intervention over time. Conclusions: These results suggest that the burst delivery may be as suitable for digital mental health interventions as the continuous delivery. The perceived difficulty of the intervention declined more steeply for the BD group, indicating that it has improved the feasibility of the positive cognitive reappraisal intervention, without hurting its efficacy. This outcome may inform the design of less burdensome interventions with improved outcomes in future research