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Viruses May 2024Treatment of hepatitis C among people who inject drugs (PWID) may be complicated by loss to follow-up and reinfection. We aimed to evaluate sustained virologic response...
Treatment of hepatitis C among people who inject drugs (PWID) may be complicated by loss to follow-up and reinfection. We aimed to evaluate sustained virologic response (SVR) and reinfection, and to validate complete pharmacy dispensation as a proxy for cure among PWID enrolled in a trial of opportunistic HCV treatment. Data were obtained by reviewing the electronic patient files and supplemented by outreach HCV RNA testing. Reinfection was defined based on clinical, behavioral, and virological data. Intention to treat SVR ≥ 4 within 2 years after enrolment was accomplished by 59 of 98 (60% [95% CI 50-70]) during intervention conditions (opportunistic treatment) and by 57 of 102 (56% [95% CI 46-66]) during control conditions (outpatient treatment). The time to end of treatment response (ETR) or SVR ≥ 4 was shorter among intervention participants (HR 1.55 [1.08-2.22]; = 0.016). Of participants with complete dispensation, 132 of 145 (91%) achieved ETR or SVR > 4 (OR 12.7 [95% CI 4.3-37.8]; < 0.001). Four cases of reinfection were identified (incidence 3.8/100 PY [95% CI 1.0-9.7]). Although SVR was similar, the time to virologic cure was shorter among intervention participants. Complete dispensation is a valid correlate for cure among individuals at risk of loss to follow-up. Reinfection following successful treatment remains a concern.
Topics: Humans; Male; Female; Reinfection; Adult; Substance Abuse, Intravenous; Sustained Virologic Response; Middle Aged; Antiviral Agents; Hepacivirus; Follow-Up Studies; Hepatitis C; Treatment Outcome; Hospitalization; RNA, Viral
PubMed: 38932151
DOI: 10.3390/v16060858 -
Viruses May 2024Hepatitis B core-related antigen (HBcrAg) reflects the activity of intrahepatic covalently closed circular DNA. HBcrAg can be detected even in chronic hepatitis B... (Review)
Review
Hepatitis B core-related antigen (HBcrAg) reflects the activity of intrahepatic covalently closed circular DNA. HBcrAg can be detected even in chronic hepatitis B patients in whom serum HBV DNA or hepatitis B surface antigen is undetectable. The HBcrAg measurement system was developed based on two concepts. One is a fully-automated and highly-sensitive HBcrAg assay (iTACT-HBcrAg) and the other is a point-of-care testing (POCT) that can be used in in resource-limited areas. iTACT-HBcrAg is an alternative to HBV DNA for monitoring HBV reactivation and predicting the development of hepatocellular carcinoma. This validated biomarker is available in routine clinical practice in Japan. Currently, international guidelines for the prevention of mother-to-child transmission recommend anti-HBV prophylaxis for pregnant women with high viral loads. However, over 95% of HBV-infected individuals live in countries where HBV DNA quantification is widely unavailable. Given this situation, a rapid and simple HBcrAg assay for POCT would be highly effective. Long-term anti-HBV therapy may have potential side effects and appropriate treatment should be provided to eligible patients. Therefore, a simple method of determining the indication for anti-HBV treatment would be ideal. This review provides up-to-date information regarding the clinical value of HBcrAg in HBV management, based on iTACT-HBcrAg or POCT.
Topics: Humans; Hepatitis B Core Antigens; Hepatitis B virus; DNA, Viral; Hepatitis B; Biomarkers; Sensitivity and Specificity; Point-of-Care Testing; Mass Screening; Carcinoma, Hepatocellular; Female; Hepatitis B, Chronic; Infectious Disease Transmission, Vertical; Viral Load; Pregnancy; Liver Neoplasms; Hepatitis B Surface Antigens
PubMed: 38932141
DOI: 10.3390/v16060848 -
Viruses May 2024Hepatitis E virus (HEV) can cause self-limiting acute and chronic hepatitis infections, particularly in immunocompromised individuals. In developing countries, HEV is...
The Full-Genome Analysis and Generation of an Infectious cDNA Clone of a Genotype 6 Hepatitis E Virus Variant Obtained from a Japanese Wild Boar: In Vitro Cultivation in Human Cell Lines.
Hepatitis E virus (HEV) can cause self-limiting acute and chronic hepatitis infections, particularly in immunocompromised individuals. In developing countries, HEV is mainly transmitted via drinking contaminated water, whereas zoonotic transmission dominates the route of infection in developed countries, including Japan. Pigs are an important reservoir for HEV infection. Wild boars, which share the same genus and species as domestic pigs, are also an HEV reservoir. During our nationwide study of HEV infection in wild boar populations in Japan, a genotype 6 (HEV-6) strain, wbJHG_23, was isolated in Hyogo Prefecture in 2023. The genomic length was 7244 nucleotides, excluding the poly(A) tract. The wbJHG_23 strain exhibited the highest nucleotide identity throughout its genome with two previously reported HEV-6 strains (80.3-80.9%). Conversely, it displayed lower similarity (73.3-78.1%) with the HEV-1-5, HEV-7, and HEV-8 strains, indicating that, although closely related, the wbJHG_23 strain differs significantly from the reported HEV-6 strains and might represent a novel subtype. The wbJHG_23 strain successfully infected the human-derived cancer cell lines, PLC/PRF/5 and A549 1-1H8 cells, suggesting that HEV-6 has the potential for zoonotic infection. An infectious cDNA clone was constructed using a reverse genetics system, and a cell culture system supporting the efficient propagation of the HEV-6 strain was established, providing important tools for further studies on this genotype. Using this cell culture system, we evaluated the sensitivity of the wbJHG_23 strain to ribavirin treatment. Its good response to this treatment suggested that it could be used to treat human infections caused by HEV-6.
Topics: Animals; Cell Line; DNA, Complementary; Genome, Viral; Genotype; Hepatitis E; Hepatitis E virus; Japan; Phylogeny; RNA, Viral; Sus scrofa; Swine; Swine Diseases
PubMed: 38932135
DOI: 10.3390/v16060842 -
Viruses May 2024Despite their small and simple structure compared with their hosts, virus particles can cause severe harm and even mortality in highly evolved species such as humans. A...
Despite their small and simple structure compared with their hosts, virus particles can cause severe harm and even mortality in highly evolved species such as humans. A comprehensive quantitative biophysical understanding of intracellular virus replication mechanisms could aid in preparing for future virus pandemics. By elucidating the relationship between the form and function of intracellular structures from the host cell and viral components, it is possible to identify possible targets for direct antiviral agents and potent vaccines. Biophysical investigations into the spatio-temporal dynamics of intracellular virus replication have thus far been limited. This study introduces a framework to enable simulations of these dynamics using partial differential equation (PDE) models, which are evaluated using advanced numerical mathematical methods on leading supercomputers. In particular, this study presents a model of the replication cycle of a specific RNA virus, the hepatitis C virus. The diffusion-reaction model mimics the interplay of the major components of the viral replication cycle, including non structural viral proteins, viral genomic RNA, and a generic host factor. Technically, surface partial differential equations (sufPDEs) are coupled on the 3D embedded 2D endoplasmic reticulum manifold with partial differential equations (PDEs) in the 3D membranous web and cytosol volume. The membranous web serves as a viral replication factory and is formed on the endoplasmic reticulum after infection and in the presence of nonstructural proteins. The coupled sufPDE/PDE model was evaluated using realistic cell geometries based on experimental data. The simulations incorporate the effects of non structural viral proteins, which are restricted to the endoplasmic reticulum surface, with effects appearing in the volume, such as host factor supply from the cytosol and membranous web dynamics. Because the spatial diffusion properties of genomic viral RNA are not yet fully understood, the model allows for viral RNA movement on the endoplasmic reticulum as well as within the cytosol. Visualizing the simulated intracellular viral replication dynamics provides insights similar to those obtained by microscopy, complementing data from in vitro/in vivo viral replication experiments. The output data demonstrate quantitative consistence with the experimental findings, prompting further advanced experimental studies to validate the model and refine our quantitative biophysical understanding.
Topics: Virus Replication; Humans; Computer Simulation; Hepacivirus; Endoplasmic Reticulum; RNA, Viral; Models, Biological; Spatio-Temporal Analysis
PubMed: 38932132
DOI: 10.3390/v16060840 -
Viruses May 2024The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple... (Review)
Review
The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.
Topics: SARS-CoV-2; Humans; COVID-19; Animals; Spike Glycoprotein, Coronavirus; Mice; Post-Acute COVID-19 Syndrome; Angiotensin-Converting Enzyme 2; Peptides; Antiviral Agents; COVID-19 Drug Treatment
PubMed: 38932130
DOI: 10.3390/v16060838 -
Viruses May 2024The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent...
The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent challenges. In addition to acute concerns, there is growing attention being given to the long COVID health consequences for survivors of COVID-19 with documented cases of cardiovascular abnormalities, liver disturbances, lung complications, kidney issues, and noticeable cognitive deficits. Recent studies have investigated the physiological changes in various organs following prolonged exposure to murine hepatitis virus-1 (MHV-1), a coronavirus, in mouse models. One significant finding relates to the effects on the gastrointestinal tract, an area previously understudied regarding the long-lasting effects of COVID-19. This research sheds light on important observations in the intestines during both the acute and the prolonged phases following MHV-1 infection, which parallel specific changes seen in humans after exposure to SARS-CoV-2. Our study investigates the histopathological alterations in the small intestine following MHV-1 infection in murine models, revealing significant changes reminiscent of inflammatory bowel disease (IBD), celiac disease. Notable findings include mucosal inflammation, lymphoid hyperplasia, goblet cell hyperplasia, and immune cell infiltration, mirroring pathological features observed in IBD. Additionally, MHV-1 infection induces villous atrophy, altered epithelial integrity, and inflammatory responses akin to celiac disease and IBD. SPIKENET (SPK) treatment effectively mitigates intestinal damage caused by MHV-1 infection, restoring tissue architecture and ameliorating inflammatory responses. Furthermore, investigation into long COVID reveals intricate inflammatory profiles, highlighting the potential of SPK to modulate intestinal responses and restore tissue homeostasis. Understanding these histopathological alterations provides valuable insights into the pathogenesis of COVID-induced gastrointestinal complications and informs the development of targeted therapeutic strategies.
Topics: Animals; Mice; COVID-19; Disease Models, Animal; Murine hepatitis virus; SARS-CoV-2; Intestinal Mucosa; Intestines; Intestine, Small; Female
PubMed: 38932125
DOI: 10.3390/v16060832 -
Viruses May 2024A number of research studies, including ours, have spotlighted exosomes as critical facilitators of viral dissemination. While hepatitis B virus (HBV) transmission...
A number of research studies, including ours, have spotlighted exosomes as critical facilitators of viral dissemination. While hepatitis B virus (HBV) transmission through exosomes has been studied, the focus on its satellite virus, the hepatitis delta virus (HDV), has been unexplored in this context. HDV, although being a defective virus, can replicate its genome autonomously within hepatocytes, independently of HBV. Investigations on Huh7 cells revealed an intriguing phenomenon: the HDV proteins, S-HDAg and L-HDAg, are transmitted between cells without a complete viral structure. Detailed analysis further revealed that the expression of these proteins not only bolstered exosome secretion but also ensured their enrichment within these vesicles. Our experimental approach utilized transfection of various plasmids to examine the role of HDV RNA and proteins in the process. One salient finding was the differential propagation of the HDV proteins S-HDAg and L-HDAg, suggesting intricate molecular mechanisms behind their transmission. Notably, the purity of our exosome preparations was monitored using markers such as TSG101 and CD81. Importantly, these exosomes were found to carry both HDV RNA and proteins, highlighting their role in HDV dissemination. This novel study underscores the role of exosomes in mediating the transmission of HDV components between hepatocytes independent of HBV. These revelations about the exosomal pathway of HDV transmission provide a foundation for the development of innovative therapeutic strategies against HDV infections.
Topics: Exosomes; Hepatitis Delta Virus; Hepatocytes; Humans; Hepatitis B virus; Virus Replication; RNA, Viral; Hepatitis D; Cell Line; Hepatitis B; Hepatitis delta Antigens
PubMed: 38932118
DOI: 10.3390/v16060825 -
Viruses May 2024The alewife ( is an anadromous herring that inhabits waters of northeastern North America. This prey species is a critical forage for piscivorous birds, mammals, and...
The alewife ( is an anadromous herring that inhabits waters of northeastern North America. This prey species is a critical forage for piscivorous birds, mammals, and fishes in estuarine and oceanic ecosystems. During a discovery project tailored to identify potentially emerging pathogens of this species, we obtained the full genome of a novel hepadnavirus (ApHBV) from clinically normal alewives collected from the Maurice River, Great Egg Harbor River, and Delaware River in New Jersey, USA during 2015-2018. This previously undescribed hepadnavirus contained a circular DNA genome of 3146 nucleotides. Phylogenetic analysis of the polymerase protein placed this virus in the clade of metahepadnaviruses (family: ; genus: ). There was no evidence of pathology in the internal organs of infected fish and virions were not observed in liver tissues by electron microscopy. We developed a Taqman-based quantitative (qPCR) assay and screened 182 individuals collected between 2015 and 2018 and detected additional qPCR positives (n = 6). An additional complete genome was obtained in 2018 and it has 99.4% genome nucleotide identity to the first virus. Single-nucleotide polymorphisms were observed between the two genomes, including 7/9 and 12/8 synonymous vs nonsynonymous mutations across the polymerase and surface proteins, respectively. While there was no evidence that this virus was associated with disease in this species, alewives are migratory interjurisdictional fishes of management concern. Identification of microbial agents using de novo sequencing and other advanced technologies is a critical aspect of understanding disease ecology for informed population management.
Topics: Animals; Genome, Viral; Phylogeny; Fish Diseases; Hepadnaviridae; Fishes; Genomics; Hepadnaviridae Infections; New Jersey
PubMed: 38932117
DOI: 10.3390/v16060824 -
Viruses May 2024Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte...
Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte entry. Hepatocellular carcinoma (HCC) ranks third in global cancer deaths, yet HDV's involvement remains uncertain. Among 300 HBV-associated HCC serum samples from Taiwan's National Health Research Institutes, 2.7% (8/300) tested anti-HDV positive, with 62.7% (5/8) of these also HDV RNA positive. Genotyping revealed HDV-2 in one sample, HDV-4 in two, and two samples showed mixed HDV-2/HDV-4 infection with RNA recombination. A mixed-genotype infection revealed novel mutations at the polyadenylation signal, coinciding with the ochre termination codon for the L-HDAg. To delve deeper into the possible oncogenic properties of HDV-2, the predominant genotype in Taiwan, which was previously thought to be less associated with severe disease outcomes, an HDV-2 cDNA clone was isolated from HCC for study. It demonstrated a replication level reaching up to 74% of that observed for a widely used HDV-1 strain in transfected cultured cells. Surprisingly, both forms of HDV-2 HDAg promoted cell migration and invasion, affecting the rearrangement of actin cytoskeleton and the expression of epithelial-mesenchymal transition markers. In summary, this study underscores the prevalence of HDV-2, HDV-4, and their mixed infections in HCC, highlighting the genetic diversity in HCC as well as the potential role of both forms of the HDAg in HCC oncogenesis.
Topics: Carcinoma, Hepatocellular; Hepatitis Delta Virus; Humans; Liver Neoplasms; Genetic Variation; Genotype; Male; Middle Aged; Carcinogenesis; Female; Taiwan; Evolution, Molecular; Virus Replication; Phylogeny; RNA, Viral; Hepatitis D; Aged; Hepatitis B virus
PubMed: 38932110
DOI: 10.3390/v16060817 -
Nutrients Jun 2024Folate is a water-soluble B vitamin involved in the synthesis of purines and pyrimidines and is one of the essential vitamins for human growth and reproduction. Folate... (Review)
Review
Folate is a water-soluble B vitamin involved in the synthesis of purines and pyrimidines and is one of the essential vitamins for human growth and reproduction. Folate deficiency due to low dietary intake, poor absorption of folate, and alterations in folate metabolism due to genetic defects or drug interactions significantly increases the risk of diseases such as neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. Recent studies have shown that folate deficiency can cause hyperhomocysteinemia, which increases the risk of hypertension and cardiovascular disease, and that high homocysteine levels are an independent risk factor for liver fibrosis and cirrhosis. In addition, folate deficiency results in increased secretion of pro-inflammatory factors and impaired lipid metabolism in the liver, leading to lipid accumulation in hepatocytes and fibrosis. There is substantial evidence that folate deficiency contributes to the development and progression of a variety of liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis, and liver cancer. Here we review key studies on the role of folate in the pathophysiology of liver diseases, summarize the current status of studies on folate in the treatment of liver diseases, and speculate that folate may be a potential therapeutic target for liver diseases.
Topics: Humans; Folic Acid; Folic Acid Deficiency; Liver Diseases; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Liver; Animals; Liver Neoplasms; Hyperhomocysteinemia; Homocysteine; Lipid Metabolism
PubMed: 38931227
DOI: 10.3390/nu16121872