Human Hepatitis Research Articles

Virus and viral components transmitted through surgical smoke; a silent danger in operating room: a systematic review

BackgroundDuring surgical procedures, heat-generating devices are widely used producing surgical smoke (SS). Since the SS can transmit infectious viruses, this systematic review was designed to investigate the potential viruses transmitted through SS.MethodsPubMed, Scopus, Web of Science, ProQuest, and Embase databases, along with Cochran Library, and Google Scholar search engine were searched systematically (by April 21, 2024). No language, place, and time restrictions were considered. All studies evaluating the SS and virus transmission, and whole investigations regarding the viral infections transmitted through SS were totally considered inclusion criteria. Besides, non-original, qualitative, case reports, case series, letters to the editor, editorial, and review studies were excluded from the analysis. This study was conducted in accordance with the PRISMA 2020 statement.ResultsTwenty-six eligible studies were selected and reviewed for data extraction. The results showed that the SS contains virus and associated components. Six types of viruses or viral components were identified in SS including papillomavirus (HPV, BPV), Human Immunodeficiency Virus (HIV), varicella zoster, Hepatitis B (HBV), SARS-CoV-2, and Oral poliovirus (OPV), which are spread to surgical team through smoke-producing devices.ConclusionsSince the studies confirm the presence of viruses, and viral components in SS, the potential risk to the healthcare workers, especially in operating room (OR), seems possible. Thus, the adoption of protective strategies against SS is critical. Despite the use of personal protective equipment (PPE), these viruses could affect OR personnel in surgical procedures.

Concanavalin-A-Induced Acute Liver Injury in Mice.

Acute liver injury is a life-threatening disease. Although immune responses are involved in the development and exacerbation of acute liver injury, the cellular and molecular mechanisms are not fully understood. Intravenous administration of the plant lectin concanavalin A (ConA) is widely used as a model of acute liver injury. ConA triggers T cell activation and cytokine production by crosslinking glycoproteins, including the T cell receptor, leading to the infiltration of myeloid cells into the liver and the subsequent amplification of inflammation in the liver. Thus, the pathogenesis of ConA-induced acute liver injury is considered a model of immune-mediated acute liver injury or autoimmune hepatitis in humans. However, the severity of the liver injury and the analyses of immune cells and non-hematopoietic cells in the liver following ConA injection are significantly influenced by the experimental conditions. This article outlines protocols for ConA-induced acute liver injury in mice and evaluation methods for liver injury, immune cells, and non-hematopoietic cells in the liver. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Induction of acute liver injury by ConA injection Basic Protocol 2: Evaluation of inflammatory cytokines in mouse plasma Basic Protocol 3: Preparation of liver sections and histological analysis of liver injury Basic Protocol 4: Preparation of liver immune cells Basic Protocol 5: Preparation of hepatocytes, endothelial cells, and hepatic stellate cells Basic Protocol 6: Flow cytometry of immune and non-hematopoietic liver cells Basic Protocol 7: Flow cytometric sorting of endothelial cells and hepatic stellate cells Basic Protocol 8: Quantitative reverse transcription polymerase chain reaction.

Immunity to Sexually Transmitted Bacterial Infections of the Female Genital Tract: Toward Effective Vaccines.

Sexually transmitted infections (STIs) caused by bacterial pathogens Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum present significant public health challenges. These infections profoundly impact reproductive health, leading to pelvic inflammatory disease, infertility, and increased susceptibility to other infections. Prevention measures, including antibiotic treatments, are limited by the often-asymptomatic nature of these infections, the need for repetitive and continual screening of sexually active persons, antibiotic resistance for gonorrhea, and shortages of penicillin for syphilis. While vaccines exist for viral STIs like human papillomavirus (HPV) and hepatitis B virus (HBV), there are no vaccines available for bacterial STIs. This review examines the immune responses in the female genital tract to these bacterial pathogens and the implications for developing effective vaccines against bacterial STIs.

Pharmacogenetic determinants of tenofovir diphosphate and lamivudine triphosphate concentrations in people with HIV/HBV coinfection.

The nucleos(t)ide analogs require phosphorylation to the pharmacologically active anabolites in cells. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) in genes that encode transporters and phosphodiesterase (PDE) enzymes involved in tenofovir (TFV), disoproxil fumarate (TDF), and lamivudine (3TC) disposition will be associated with concentrations of their phosphate anabolites and virologic response. Individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection receiving TDF/3TC-containing antiretroviral therapy were enrolled. Steady-state TFV diphosphate (TFV-DP) and 3TC triphosphate (3TC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spot samples were quantified. The relationship between genetic variants and TFV-DP and 3TC-TP concentrations as well as with virologic response were examined using multivariable linear regression. Of the 136 participants (median age 43 years; 63% females), 6.6% had HBV non-suppression, and 7.4% had HIV non-suppression. The multidrug resistance protein 2 (encoded by ABCC2 rs2273697) SNP was associated with 3TC-TP concentrations in PBMCs. The human organic anion transporter-1 (encoded by SLC28A2) rs11854484 SNP was associated with HIV non-suppression, and when evaluated together with SNPs with marginal associations (ABCC2 rs717620 and PDE1C rs30561), participants with two or three variants compared to those with none of these variants had an adjusted odds ratio of 48.3 (confidence interval, 4.3-547.8) for HIV non-suppression. None of the SNPs were associated with HBV non-suppression. Our study identified ABCC2 SNP to be associated with 3TC-TP concentrations in PBMCs. Also, a combination of genetic variants of drug transporters and PDE was associated with HIV non-suppression.

Markers of CD4⁺ AND CD8⁺ T-cell exhaustion in hiv/hcv coinfected immunological non-responders to antiretroviral therapy

Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a risk factor for immunological non-response to antiretroviral therapy. In cases of immunological non-response, HIV viral load suppression occurs without an increase in CD4⁺ T-cell counts, heightening the risk of morbidity and mortality in infected individuals. T-cell exhaustion may hinder their regeneration in immunological non-responders. This study aimed to identify markers of CD4⁺ and CD8⁺ T-cell exhaustion in HIV/HCV coinfected immunological non-responders. The study examined three clinical groups: 1) HIV/HCV coinfected immunological non-responders (CD4⁺ T-cells 350/µl blood; n = 9), 2) HIV/HCV coinfected individuals with a standard response to therapy (CD4⁺ T-cells 500/µl blood; n = 9), and 3) relatively healthy volunteers without HIV and HCV infections (n = 9). Ex vivo, the number of CD4⁺ and CD8⁺ T-cells expressing the inhibitory receptor PD-1 was determined using multi-color flow cytometry. In the 7-day in vitro experiment, cell cultures were stimulated with phytohemagglutinin. The number of dying proliferated CD4⁺ and CD8⁺ T-cells (CFSElowZombieUV+) was determined using multi-color flow cytometry. The amount of interleukin-2 in the culture supernatants was measured using an enzyme-linked immunosorbent assay. It was found that in HIV/HCV coinfected immunological non-responders, there was a higher number of CD4⁺ and CD8⁺ T-cells expressing PD-1, a phenotypic marker of exhaustion, compared to the other two groups. Furthermore, the frequency of dying dividing T-cells was higher in immunological non-responders, with an increase in CD4⁺ T-cells but not CD8⁺ T-lymphocytes. Similarly, a decrease in interleukin-2 production was found in stimulated T-cells of HIV/HCV coinfected immunological non-responders in the CD4⁺ T-cell pool, but not in CD8⁺ T-lymphocytes. Thus, in HIV/HCV coinfected immunological non-responders, CD4⁺ T-cells appear exhausted both phenotypically and functionally. While CD8⁺ T-cells express inhibitory receptors, they do not show functional impairments. It appears that the specialized therapy for HIV/HCV coinfected immunological non-responders should aim to improve CD4⁺ T-cell function.

Design of Hepatitis C Protease Inhibitors Based on Knottin Fold

AbstractKnottins are very stable peptides (also called miniproteins) containing approximately 30 amino acid residues. Their structures are stabilized by three disulfide bonds forming a characteristic ‘pseudo‐knotted’ structure. This research was devoted to the design of potential inhibitors of human hepatitis C (HCV) NS3 protease by means of knottin fold using loop grafting, amino acid residues replacements and L/D amino acid epimerization. The initial structure used for design was a trypsin inhibitor from Momordica cochinchinensis seeds, MCOTI‐II. Modifications of the knottin template for optimization of the NS3 protease‐peptide interaction included deletion of several residues from the N‐terminus, replacement of residues in‐ and outside the inhibitor loop and replacement of certain L‐amino acids by their D‐stereoisomers. Stability of modified knottins and their complexes with HCV protease were evaluated by molecular dynamics simulation. Binding energy values for protein‐knottin complexes were calculated by MM‐GBSA method. The designed modified knottin characterized by the highest stability of the complex with HCV NS3 protease, was proposed for further experimental testing.

Immune reconstitution and cidofovir administration rescue human adenovirus hepatitis after allogeneic hematopoietic cell transplantation

Human adenovirus infection (HAdV) may be fatal in patients undergoing allogeneic hematopoietic cell transplantation (HCT). Cidofovir is effective in only a part of the post-HCT HAdV infection. Therefore, posttransplant immune reconstitution is important for HAdV clearance. We describe the detailed immune reconstitution and response of adenovirus-specific T cells in a patient with inborn errors of immunity who had disseminated HAdV infection with hepatitis post-HCT and was treated with cidofovir.Though the patient received cidofovir for only 19 days starting from Day 72 after HCT because of renal dysfunction, we observed T-cell reconstitution, a decrease in HAdV copy number, and amelioration of the symptoms of HAdV infection after Day 90. We initially observed expanded NK and CD8+CD45RO+ memory subsets and later gradual increase of naïve T cells eveloped after cessation of cidofovir treatment. An increase in adenovirus-specific IFN-γ secretion from 2 to 4 months after HCT was confirmed by ELISpot assay.The progression of immune reconstitution and cidofovir treatment are considered to have contributed to survival in this patient. Optimization of transplantation methods, prompt appropriate antiviral medication, and virus-specific T-cell therapy would be necessary as the better strategy for systemic HAdV infection.

IFNγ initiates TLR9-dependent autoimmune hepatitis in DNase II deficient mice.

Patients with biallelic hypomorphic mutation in DNASE2 develop systemic autoinflammation and early-onset liver fibrosis. Prior studies showed that Dnase2 -/- Ifnar -/- double knockout (DKO) mice develop Type I IFN-independent liver inflammation, but immune mechanisms were unclear. We now show that DKO mice recapitulate many features of human autoimmune hepatitis (AIH), including periportal and interstitial inflammation and fibrosis and elevated ALT. Infiltrating cells include CD8+ tissue resident memory T cells, type I innate lymphoid cells, and inflammatory monocyte/macrophage cells that replace the Kupffer cell pool. Importantly, TLR9 expression by bone marrow-derived cells is required for the the development of AIH. TLR9 is highly expressed by inflammatory myeloid cells but not long-lived Kupffer cells. Furthermore, the initial recruitment of TLR9 expressing monocytes and subsequent activation of lymphocytes requires IFNγ signaling. These findings highlight a critical role of feed forward loop between TLR9 expressing monocyte-lineage cells and IFNg producing lymphocytes in autoimmune hepatitis.

Deviated binding of anti-HBV nucleoside analog E-CFCP-TP to the reverse transcriptase active site attenuates the effect of drug-resistant mutations

While certain human hepatitis B virus-targeting nucleoside analogs (NAs) serve as crucial anti-HBV drugs, HBV yet remains to be a major global health threat. E-CFCP is a 4′-modified and fluoromethylenated NA that exhibits potent antiviral activity against both wild-type and drug-resistant HBVs but less potent against human immunodeficiency virus type-1 (HIV-1). Here, we show that HIV-1 with HBV-associated amino acid substitutions introduced into the RT’s dNTP-binding site (N-site) is highly susceptible to E-CFCP. We determined the X-ray structures of HBV-associated HIV-1 RT mutants complexed with DNA:E-CFCP-triphosphate (E-CFCP-TP). The structures revealed that exocyclic fluoromethylene pushes the Met184 sidechain backward, and the resultant enlarged hydrophobic pocket accommodates both the fluoromethylene and 4′-cyano moiety of E-CFCP. Structural comparison with the DNA:dGTP/entecavir-triphosphate complex also indicated that the cyclopentene moiety of the bound E-CFCP-TP is slightly skewed and deviated. This positioning partly corresponds to that of the bound dNTP observed in the HIV-1 RT mutant with drug-resistant mutations F160M/M184V, resulting in the attenuation of the structural effects of F160M/M184V substitutions. These results expand our knowledge of the interactions between NAs and the RT N-site and should help further design antiviral NAs against both HIV-1 and HBV.

Antiviral Effect of Ferula Plants and their Potential for Treatment of COVID-19: A Comprehensive Review.

Viral diseases have always been a threat to mankind throughout history, and many people have lost their lives due to the epidemic of these diseases. In recent years, despite the progress of science, we are still witnessing a pandemic of dangerous diseases such as COVID-19 all over the world, which can be a warning for humanity. Ferula is a genus of flowering plants commonly found in Central Asia, and its species have shown antiviral activity against a variety of viruses, including respiratory syncytial virus, Herpes simplex virus type 1, influenza, human immunodeficiency virus, hepatitis B, and coronaviruses. In this study, we intend to review the antiviral effects of Ferula plants, emphasizing the therapeutic potential of these plants in the treatment of COVID-19. Google, PubMed, Web of Science, and Scopus databases were searched to review the relevant literature on the antiviral effect of Ferula or its isolated compounds. The search was performed using the keywords Ferula, antiviral, Coronaviruses, respiratory syncytial virus, Herpes simplex virus type 1, influenza, human immunodeficiency virus, and hepatitis B. According to the reviewed articles and available scientific evidence, it was determined that the plants of this genus have strong antiviral effects. Also, clinical studies have shown that some species, such as Ferula assa-foetida, can be used effectively in the treatment of COVID-19. Ferula plants have inhibitory effects on various viruses, making them an attractive alternative to conventional antiviral agents. Therefore, these plants are a natural source of valuable compounds that can help us fight infectious diseases.

Knowledge, Practices and Attitude of Pregnant Women on Prevention and Transmission of HIV, Hepatitis B and C With Respect to Educational Level among Pregnant Women Visiting Health Centers at the Mifi Health District in Cameroon

Purpose: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) , hepatitis C virus are causes of significant morbidity and mortality across the World .HIV and HBV&HCV are blood-borne viruses transmitted usually through sexual contact and use of unsterilized needles. Their similar means of transmission increases the risk of contracting both infections concurrently. This study was aimed at assessing the knowledge, practices and attitude of pregnant women on prevention and transmission of HIV, hepatitis B and C with respect to educational level at the Mifi health district. Methodology: This study was a descriptive cross sectional study involving pregnant women who visited different health centers with the Mifi health district between the month of January to june 2023. Sampling was done by convenience Data was analysed using version 20.0. and the data was presented in tables and bar graphs, meanwhile the pearson chi square test was used to compare variables under investigation at a confidence interval of 95%, providing a 5% error margin. Descriptive values were expressed as the frequency, percentage, and mean ± standard deviation (SD). Findings: Out of the 467 participants, 80.73% were within the poor knowledge range whereas 12.63% showed good knowledge (while 6.63 recorded excellent knowledge scores. 44.96% were within the poor practice range while 55.03% showed good practice. majority showed poor attitude toward transmission and prevention of HIV, HBV and HCV as only 18(3.85%) were willing to meet the doctor if they were diagnosed of any of the above mention infections meaning 449 (96.14%) will embrace fear and sadness. Majority of pregnant women in this study had good knowledge regarding prevention and transmission of HIV,HBV and. Irrespective of the knowledge, practices and attitude of the participants were generally poor at the Mifi health district in Cameroon. Unique Contribution to Theory, Practice and Policy: This research have come to set standard in health facilities in the mifi health district by proving beyond doubt that pregnant women are co infected with both HIV,HBV, and HCV and giving the poor attitude and practices among women that fuel the transmissions of these infections, we stand to advocate that all women presenting for ANC, should be compulsorily tested for HIV,HBV and HCV and equally much education on the transmission mode of these infections by the nurses should be implemented. This study have saved as an eye opener to policy makers to impost the testing of HIV, HBV and HCV during every first ANC visit and possibly two weeks before delivery.

Antiviral potential of spirulina in individuals with human immunodeficiency virus or Hepatis C virus infections: A systematic review and meta-analysis

BackgroundSpirulina, a cyanobacterium or blue-green algae that contains phycocyanin, nutritional supplementation has been evaluated in patients living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) due to its antiviral properties. This supplementation may be beneficial in low resource settings when awaiting antiretroviral therapy (ART) for HIV. This review aimed to evaluate the effectiveness of Spirulina supplement in antiviral-naïve HIV- and HCV-infected patients by assessing its immunological effect (Cluster of Differentiation 4 or CD-4 T-cell count) and disease progression (viral load). MethodsWe searched PubMed, Cochrane Library, Scopus, and Web of Science from inception through January 23, 2024. Two authors independently performed the study selection, data extraction, and risk of bias assessment. We pooled data by using a random-effects model and evaluated publication bias by a funnel plot. ResultsWe identified 5552 articles, 5509 excluded at the title and abstract stage with 44 studies making it to the full text review. Of these 6 studies met the eligibility for inclusion in the final analysis as follows:4 randomized controlled trials (RCTs) and 2 non-RCTs. The pooled results of the Spirulina intervention found significant improvements in biomarkers of clinical outcomes, viral load (VL) and CD4 T-cell (CD4) counts, in participants of the treatment group compared to controls; the VL had an overall Cohen’s d effect size decrease of -2.49 (-4.80, -0.18) and CD4 had an overall effect size increase of 4.09 (0.75, 7.43). [Cohen’s d benchmark: 0.2 = small effect; 0.5 = medium effect; 0.8 = large effect]. ConclusionsFindings from this systematic review showed a potential beneficial effect of Spirulina supplementation in HIV- and HCV-infected patients by increasing CD4 counts and decreasing viral load. However, further research in larger controlled clinical trials is needed to fully investigate the effect of this nutritional supplement on clinically relevant outcomes, opportunities for intervention, optimal dose, and cost-benefit of Spirulina supplementation.

Assessment of liver fibrosis by transient elastography among human immunodeficiency virus/hepatitis B virus and hepatitis B virus-mono-infected patients on tenofovir therapy in Jos, Nigeria

Objectives: Chronic hepatitis B (CHB) infection, both in human immunodeficiency virus (HIV) coinfection and hepatitis B virus (HBV)-mono-infection, is associated with a risk of progression to chronic liver disease. In Nigeria, there is a paucity of data on transient elastography (TE) in HIV/HBV and HBVmono-infected patients. This study aimed at assessing liver fibrosis using TE in relation to liver function biomarkers and HBV deoxyribonucleic acid (DNA) among HIV/HBV and HBV-mono-infected patients on long-term antiviral therapy. Material and Methods: This was a cross-sectional study among HBV–HIV and HBV-mono-infected adult’s patients receiving a tenofovir-containing antiretroviral and mono-tenofovir ≥12 months at three selected tertiary hospitals in Jos Metropolis from February 2018 to May 2019, after obtaining ethical approval from the Institutional Review Boards and informed consents. The patients’ HBV DNA, platelet count, hematological, and biochemical parameters were assessed, and liver stiffness was measured by TE in kilopascals (kPa), and valid TE measurements were interpreted as: normal (F0– 1 0–4), minimal fibrosis (F2 5–7.4), moderate (F3 7.5.9.4), and severe fibrosis and cirrhosis (F4 ≥9.5). Results: A total of 101 (50 HIV/HBV and 51 HBV-mono-infected) were enrolled during the study period, comprising 42.6% males and 57.4% females. The median age interquartile range among HIV/HBV coinfected was 40.5 years (36.0–45.3) and HBV-mono-infected was 41.0 years (35.0–49.0). The median platelet count was low in the HBV-mono-infected group 195 × 109/L (168–257), P = 0.034. The overall prevalence of severe liver fibrosis (≥9.5 kPa) was 13/101 (13.0%), and among HIV/HBV-coinfected and HBV-mono-infected patients, the prevalence was 4/50 (8.0%) and 9/51 (17.6%), respectively. The plasma HBV DNA was <20 copies/mL in 38/50 (76.0%) HIV/HBV coinfected individuals and in 30/51 (58.8%) of HBV-mono-infected patients. In addition, 10/50 (20.0%) HIV/HBV coinfected and 19/50 (37.3%) HBV-mono-infected patients had plasma HBV DNA levels of 20–20,000 copies/mL. In the case of HIV/HBV coinfection, the prevalence of severe fibrosis (≥9.5) was 4/50 (8.0%), while in HBV-mono-infected patients, the prevalence was was 9/51 (17.6%). The overall prevalence of thrombocytopenia was observed in 4/101 cases (3.9%): 1/50 (2.0%) in HIV/HBV coinfected individuals and 3/51 (5.9%) in HBV-mono-infected patients. Conclusion: Severe liver fibrosis as observed among HIV/HBV-coinfected and HBV-mono-infected patients in this study affirmed the necessity of routine HBV screening in clinics and it highlights the immense potentials of tenofovir therapy in the treatment of CHB patients.

Validity of dried blood spot testing for sexually transmitted and blood-borne infections: A narrative systematic review.

Testing for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) using dried blood spot (DBS) specimens has been an integral part of bio-behavioural surveillance in Canada for almost two decades, though less is known regarding the use of DBS in surveillance of other sexually transmitted and blood-borne infections (STBBI). A systematic review was conducted using a peer-reviewed search strategy to assess the current evidence regarding the validity of STBBI testing using DBS specimens. Eligibility criteria included studies reporting use of DBS specimens for STBBI testing with either commercially available or "in-house" tests in populations 15 years of age or older. Studies reporting a measure of validity such as sensitivity, specificity, positive and negative predictive values were eligible for inclusion. Quality of studies and risk of bias were assessed using the QUADAS-2 tool. A total of 7,132 records were identified. Of these, 174 met the criteria for inclusion. Among the studies that reported validity measures, a substantial proportion demonstrated high sensitivity (≥90%) in 62.5% of cases (N = 334/534 sensitivity measurements), and high specificity (≥90%) was observed in 84.9% of instances (N = 383/451 specificity measurements). However, the quality of the studies varied greatly. Our findings support the validity of the use of DBS specimens in STBBI testing where sufficient evidence was available, but validity is highly dependent on thorough method development and validation.

Nanopore efficiently identifies hepatitis D virus antigens in vitro assay

Chronic hepatis B with HDV (Hepatitis D Virus) coinfection is considered as one of the most serious forms of human viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. However, the high GC ratios in HDV genome and the same surface antigen protein HBsAg (Hepatitis B surface Antigen) in virus particles assembly make it hard (or ignored) to diagnose HDV co-infection with HBV (Hepatitis B Virus) using traditional methods (i.e., antibody-surface antigen reaction), further limit to build epidemiologic information on HDV. Thus, developing efficient detection for key pathogenetic molecules of HDV becomes key experimental questions for HDV diagnosis. In these key molecules, specific HDAgs (Hepatitis D Antigens, including large and small HDAgs) are the solitary ribonucleoproteins encoded by HDV genome, which function in viral life cycle in significant ways. Herein, we propose a direct and precise detection for large and small HDAgs using nanopore sensor in asymmetric ionic liquids electrolyte condition. What's as obvious from nanopore measurement for either antigen is that the results allow discriminate large and small HDAgs as well as antigen-ribozyme complex in serological assay. More importantly, it is ascertained by nanopore test that HDAgs can be efficiently distinguished with HBsAg in HBV-infected cells, enabling simultaneous identification of HBV- and HDV-infected cells. In conclusion, the proposed nanopore can provide specific and efficient detection of physiological indicators for different hepatitis virus infections at molecular and cellular levels, and should benefit severer HBV/HDV co-infection diagnosis and therapy.

Development of fatty liver disease model using high cholesterol and low choline diet in white leghorn chickens

Nonalcoholic fatty liver disease (NAFLD), which shows similar symptoms as fatty liver hemorrhage syndrome (FLHS) in chickens, is the most common cause of chronic liver disease and cancer in humans. NAFLD patients and FLHS in chickens have demonstrated severe liver disorders when infected by emerging strains of human hepatitis E virus (HEV) and avian HEV, respectively. We sought to develop a fatty liver disease chicken model by altering the diet of 3-week-old white leghorn chickens. The high cholesterol, and low choline (HCLC) diet included 7.6% fat with additional 2% cholesterol and 800 mg/kg choline in comparison to 5.3% fat, and 1,300 mg/kg choline in the regular diet. Our diet induced fatty liver avian model successfully recapitulates the clinical features seen during NAFLD in humans and FLHS in chickens, including hyperlipidemia and hepatic steatosis, as indicated by significantly higher serum triglycerides, serum cholesterol, liver triglycerides, cholesterol, and fatty acids. By developing this chicken model, we expect to provide a platform to explore the role of lipids in the liver pathology linked with viral infections and contribute to the development of prophylactic interventions.

Going (Anti)Viral: Improving HIV and HCV Screening and HPV Vaccination in Primary Care

Human immunodeficiency virus (HIV) and hepatitis C (HCV) screening and human papillomavirus (HPV) vaccine uptake remain suboptimal. To improve HIV and HCV screening and HPV vaccination, the authors implemented a quality improvement project in three southwestern Pennsylvania family medicine residency practices. From June 1 to November 30, 2021, participating practices used universal screening and vaccination guidelines and chose from multiple strategies at the office (for example, standing orders), provider (for example, multiple forms of provider reminders), and patient (for example, incentives) levels derived from published literature and tailored to local context. Age-eligible patients for each recommendation with at least one in-person office visit during the intervention period were included. To assess the interventions' effect, the authors obtained testing and vaccination data from the electronic health record for the intervention period, contrasted it with identical data from June 1 to November 30, 2020, and used logistic regression controlling for patient age, sex, and race to determine differences in screening and vaccination between intervention and baseline periods. A total of 14,920 and 15,523 patients were eligible in the baseline and intervention periods, respectively. Following the intervention, HIV lifetime screening but not first-time screening for patients 13-64 years old was significantly higher (78.9% vs. 76.1%, p = 0.004, and 39.6% vs. 36.6%, p = 0.152, respectively, adjusted odds ratio [aOR] 1.21, 95% confidence interval [CI] 1.06-1.38). HCV lifetime screening for patients 18-79 years old was significantly higher postintervention (62.5% vs. 53.5%, p < 0.001, aOR 1.51, 95% CI 1.4-1.64). For patients 9-26 years old, no change in HPV initiation was observed, but the percentage of patients who completed their HPV vaccinations in the observed period was significantly higher postintervention (7.0% vs 4.6%, p = 0.006, aOR 1.58, 95% CI 1.14-2.2). During the postintervention period, the researchers identified 0 new HIV diagnoses and 48 HCV diagnoses (19 eligible for treatment). Family medicine residency office-based multistrategy efforts appear to successfully increase patient uptake of HIV and HCV screenings and maintain HPV vaccination rates.

Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication

Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient. These insertions increase viral replication while not affecting sensitivity towards ribavirin in a subgenomic replicon assay. All insertions contain a predicted nuclear localization sequence and alanine scanning mutagenesis of lysine residues in the HVR influences viral replication. Sequential replacement of lysine residues additionally alters intracellular localization in a fluorescence dye-coupled construct. Furthermore, distinct sequence patterns outside the HVR are identified as viral determinants that recapitulate the enhancing effect. In conclusion, patient-derived insertions can increase HEV replication and synergistically acting viral determinants in and outside the HVR are described. These results will help to understand the underlying principles of viral adaptation by viral- and host-sequence snatching during the clinical course of infection.

Evidences support that dengue virus can impart broad-spectrum immunity against betacoronaviruses in dengue endemic regions.

COVID-19 tended to be less aggressive in dengue endemic regions. Conversely, dengue cases plummeted in dengue endemic zones during the active years of the pandemic (2020-2021). We and others have demonstrated serological cross-reactivity between these two viruses of different families. We further demonstrated that COVID-19 serum samples that were cross-reactive in dengue virus (DV) serological tests, "cross-neutralized" all DV serotypes in Huh7 cells. Here we showed by co-immunoprecipitation (Co-IP) and atomic force microscopy (AFM) imaging that severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 (SARS-CoV-2) spike (S) protein subunit S1 and S2 monoclonal antibodies can indeed, bind to DV particles. Likewise, DV envelope antibodies (DV E Abs) showed high docking frequency with other human pathogenic beta-CoVs and murine hepatitis virus-1 (MHV-1). SARS-CoV-2 Ab didn't show docking or Co-IP with MHV-1 supporting poor cross-protection among CoVs. DV E Abs showed binding to MHV-1 (AFM, Co-IP, and immunofluorescence) and prepandemic dengue patients'serum samples even "cross-neutralized" MHV-1 plaques in cell culture. Furthermore, dengue serum samples showed marked inhibition potential in a surrogate virus-based competitive enzyme-linked immunosorbent assay, used for determining neutralizing Abs against SARS-CoV-2 S protein receptor-binding domain in COVID-19 serum samples. We therefore, provide multiple evidence as to why CoVs are epidemiologically less prevalent in highly dengue endemic regions globally.

In Vitro Virucidal Activity of Different Essential Oils against Bovine Viral Diarrhea Virus Used as Surrogate of Human Hepatitis C Virus.

The hepatitis C virus (HCV) is a major hepatotropic virus that affects humans with increased risk of developing hepatocellular carcinoma. The bovine viral diarrhea virus (BVDV) causes abortion, calf mortality and poor reproductive performance in cattle. Due the difficulties of in vitro cultivation for HCV, BVDV has been used as surrogate for in vitro assessment of the efficacy of antivirals. Essential oils (EOs) display antiviral and virucidal activity on several viral pathogens. In this study, the virucidal activity of five EOs, Salvia officinalis L. EO (SEO), Melissa officinalis L. EO (MEO), Citrus lemon EO (LEO), Rosmarinus officinalis L. EO (REO) and Thymus vulgaris L. EO (TEO) against BVDV was evaluated in vitro at different concentrations for several time contacts. MEO and LEO were able to considerably inactivate BVDV with a time- and dose-dependent fashion. MEO and LEO at the highest concentrations decreased viral titer by 2.00 and 2.25 log10 TCID50/50 μL at 8 h contact time, respectively. SEO, REO and TEO displayed mild virucidal activity at the highest concentrations for 8 h contact times. In this study, the virucidal efficacies of MEO and LEO against BVDV were observed regardless of compound concentration and contact time. Further studies are needed to confirm the potential use of MEO and LEO as surface disinfectants.