Virus Infection Research Articles

Exploring the anti-inflammatory potential of phytochemicals against STING::TBK1 pathway

ABSTRACT Viral illnesses frequently cause excessive inflammation in the body, which adds to the severity of symptoms and problems. Understanding and regulating this inflammatory response is critical for successful viral infection management and therapy. It is traditional Ayurvedic understanding to reduce inflammation with formulations of Tulsi, Dalchini, Sunthi, and Krishan mirch. Using computer-aided drug discovery methodologies, this study aims to find phytochemicals that interact with TBK1 and are likely to have this anti-inflammatory effect. Molecular docking results revealed that Oleanolic acid, Astiaticoside A, Cepharadione A, Proanthrocyanidin, and Alpha carotene had binding scores of −8.1 kcal/mol, −7.8 kcal/mol, −6.8 kcal/mol, −6.75 kcal/mol, and −6.8 kcal/mol against TBK1, respectively. 20 ns MD simulations of TBK1 in complex with phytochemicals were performed to evaluate complex stability and protein conformational changes. The simulations showed stable complexes with favourable energy profiles, as evidenced by characteristics such as RMSD, RMSF, Rg, and hydrogen bonding. The MM-PBSA analysis produced precise binding affinity estimates. This work emphasises the potential of these phytochemicals and the need for additional in vitro and in vivo validation.

TianTan Vaccinia Virus-based EBV vaccines targeting both latent and lytic antigens elicits potent immunity against lethal EBV challenge in humanized mice.

AbstractEpstein-Barr virus (EBV) infection has been related to multiple epithelial cancers and lymphomas. Current efforts in developing a prophylactic EBV vaccine have focused on inducing neutralizing antibodies. However, given the lifelong and persistent nature of EBV infection following primary infection, it is rationalized that an ideal vaccine should elicit both humoral and cellular immune responses targeting multiple stages of the EBV lifecycle. This study used a DNA vector and a TianTan vaccinia virus to express key EBV antigens, including BZLF1, EBNA1, EBNA3B, and gH/gL, to generate multi-antigen vaccines. The multi-antigen vaccine expressing all four antigens and the multi-antigen vaccine expressing BZLF1, EBNA1, and EBNA3B showed comparable protection effects and prevented 100% and 80% of humanized mice, respectively, from EBV-induced fatal B cell lymphoma by activating BZLF1, EBNA1, and EBNA3B specific T cell. The vaccine expressing lytic protein BZLF1 elicited stronger T cell responses and conferred superior protection compared to vaccines targeting single latent EBNA1 or EBNA3B. The vaccine solely expressing gH/gL exhibited no T cell protective effects in our humanized mice model. Our study implicates the potential of EBV vaccines that induce potent cellular responses targeting both latent and lytic phases of the EBV life cycle in the prevention of EBV-induced B cell lymphoma.

A critical review on the active anti-viral metabolites of bioprospecting traditionally used plant species from semi-arid regions of the subcontinent.

Plants are crucial medicinal resources, with 80 % of people relying on them for primary healthcare. The search for natural antiviral compounds is increasing, especially in semi-arid ecosystems where abiotic stress promotes the production of beneficial secondary metabolites. This review highlights semi-arid plants with the potential as functional foods to combat viral diseases and other illnesses. Literature was searched in databases like ScienceDirect to gather information on novel compounds from stress-tolerant semi-arid plant species. These compounds have potential uses in treating viral infections and other health issues such as diabetes and high blood pressure. The review screened 61 semi-arid plants known for their antiviral metabolites. Eight plants were identified with novel antiviral compounds. Key metabolites include agathisflavone, pectic arabinogalactan, azadirachtin, aloin, aloe-emodin, aloesaponarin I, allicin, terpenoids, chlorogenic acids, curcumin, chromones, β-sitosterol, lupeol, oleuropein, carissol, β-amyrin, and ∆-9-tetrahydrocannabinol. Stress-tolerant semi-arid plants are significant sources of metabolites for treating infectious diseases and boosting immune systems. Further research on these metabolites in animal models is needed to verify their efficacy for treating human diseases during endemic and pandemic outbreaks, such as COVID-19.

Novel Compound Heterozygous Variants in the FAS Gene Lead to Fetal Onset of Autoimmune Lymphoproliferative Syndrome (ALPS).

FAS gene defects lead to autoimmune lymphoproliferative syndrome (ALPS), which is often inherited in an autosomal dominant and rarely in an autosomal recessive manner. We report a case of a newborn girl with novel compound heterozygous variants in FAS and reveal the underlying mechanism. Whole-exome sequencing (WES) was used to identify pathogenic variants. Multiparametric flow cytometry analysis, phosflow analysis, and FAS-induced apoptosis assays were used to explore the effects of the variants on FAS expression, apoptosis, and immunophenotype. The HEK293T cells were used to assess the impact of the variants on protein expression and FAS-induced apoptosis. The patient was born with hepatosplenomegaly, anemia, and thrombocytopenia. She also experienced COVID-19, rotavirus infection, herpes simplex virus infection, and severe pneumonia. The proportion of double-negative T cells (DNTs) was significantly elevated. Novel FAS compound heterozygous variants c.310T > A (p.C104S) and c.702_704del (p.T235del) were identified. The apoptotic ability of T cells was defective, and FAS expression on the surface of T cells was deficient. The T235del variant decreased FAS expression, and the C104S protein remained in the endoplasmic reticulum (ER) and could not translocate to the cell surface. Both mutations resulted in loss-of-function in terms of FAS-induced apoptosis in HEK293T cells. The DNTs were mainly terminally differentiated T (TEMRA) and CD45RA+HLA-DR+, with high expression of CD85j, PD-1, and CD57. The percentage of Th1, Tfh, and autoreactive B cells were significantly increased in the patient. The abnormal immunophenotyping was partially attenuated by sirolimus treatment. We identified two variants that significantly affect FAS expression or localization, leading to early disease onset of in the fetus. Abnormalities in the mTOR pathway are associated with a favorable response to sirolimus.

Acute onset psychiatric diseases after SARS-CoV-2 virus infection among pediatric patients

BackgroundPsychiatric symptoms directly associated with SARS-CoV-2 virus infection have been reported sporadically in children. More cases of new-onset psychosis without severe cardinal symptoms, altered consciousness level, and psychogenic drug usage would offer compelling grounds for the association between the virus infection and psychosis.MethodsWe collected the clinical data of pediatric patients with new onset psychiatric symptoms after the SARS-CoV-2 virus infection from December 2022 to Feb 2023 and followed up with them for 1 year. These children did not have severe respiratory, cardiovascular, or systemic symptoms. They were not given psychogenic drugs. We also searched Pubmed to identify previously reported acute onset psychiatric cases related to SARS-CoV-2 virus infection in children. We summarized these patients’ clinical symptoms, laboratory examination, treatment, and prognosis.ResultsWe reported 11 new cases of psychiatric disease directly related to SARS-CoV-2 virus infection and reviewed 12 previously reported cases among children and adolescents. They had various psychiatric symptoms within 3 weeks after the virus infection. Brain MRI and EEG recording did not reveal remarkable abnormalities. The cerebrospinal fluid analysis (CSF) could find increased protein, immunoglobulin, and IL-8 levels, disrupted blood–brain barrier, and positive oligoclonal band in a minority of the patients. Most of the patients had good outcomes.ConclusionNew-onset psychiatric symptoms directly related to SARS-CoV-2 virus infection are not rare phenomena among pediatric patients. CSF tests support the presence of central immune responses in some patients. Although these patients received different treatments, most of them had good prognoses.

Phytochemistry, Mechanisms, and Preclinical Studies of Echinacea Extracts in Modulating Immune Responses to Bacterial and Viral Infections: A Comprehensive Review

Background: Echinacea species, particularly Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida, are renowned for their immunomodulatory, antibacterial, and antiviral properties. Objectives: This review explores the mechanisms by which echinacea herbal extracts modulate immune responses, focusing on their effects on both innate and adaptive immunity in bacterial and viral infections. Results: Key bioactive compounds, such as alkamides, caffeic acid derivatives, flavonoids, and polysaccharides, contribute to these effects. These compounds enhance immune cell activity, including macrophages and natural killer cells, stimulating cytokine production and phagocytosis. The antibacterial activity of echinacea against respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila) and skin pathogens (Staphylococcus aureus, Propionibacterium acnes) is reviewed, as well as its antiviral efficacy against viruses like herpes simplex, influenza, and rhinovirus. Echinacea’s potential as a complementary treatment alongside conventional antibiotics and antivirals is discussed, particularly in the context of antibiotic resistance and emerging viral threats. Conclusions: Challenges associated with variability in phytochemical content and the need for standardized extraction processes are also addressed. This review provides a comprehensive overview of echinacea’s therapeutic potential and outlines future directions for research, including clinical trials and dosage optimization.

AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation

Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.

Comparative study on the epidemiological characteristics and hazards of respiratory syncytial virus and influenza virus infections among elderly people

ObjectiveTo investigate the epidemiological characteristics and infections of respiratory syncytial virus (RSV) and influenza viruses in hospitalized elderly patients with respiratory tract infections in Suzhou City, China, and to compare the differences in clinical characteristics and economic burden associated with these two infections.MethodsIn this prospective study, pathogenetic testing and clinical data for hospitalized patients aged 60 years and older with respiratory tract infections were collected in five hospitals through stratified cluster sampling from December 2023 to May 2024. Comparative study on epidemic characteristics, clinical features and costs of cases who infected RSV alone and influenza alone were conducted.ResultsAmong 1,894 cases included, the RSV positivity rate was 5.91% during the 2023–2024 winter-spring season, while the influenza positivity rate was 9.61%. RSV-B was the predominant subtype of RSV, and influenza A (primarily H3N2) was the dominant strain among the influenza-positive cases. Compared with cases infected influenza virus alone, those infected RSV alone had lower occurrence frequency of fever (18.8% vs. 35.7%, P = 0.004), higher occurrence frequency of complications of lower respiratory tract infections (70.8% vs. 54.8%, P = 0.011), higher direct medical costs ($996.2 vs. $841.1, P = 0.017) and total costs ($1019.7 vs. $888.1, P = 0.036). RSV single infection is more common in female cases (P = 0.007) and diabetic cases (P = 0.007) than influenza virus single infection.ConclusionsDuring the winter and spring months, RSV is the second most common pathogen after influenza virus among older adults hospitalized for respiratory infections in Suzhou, China. Patients infected RSV are more likely to develop complications with lower respiratory tract infections and have higher medical costs than the influenza. RSV infection in the elderly should be emphasized, especially in female patients and diabetic patients.

Arterial Thrombosis in Acute Respiratory Infections: An Underestimated but Clinically Relevant Problem

During the COVID-19 pandemic, there was increased interest in the issue of thrombotic complications of acute respiratory infections. Clinical reports and pathological studies have revealed that thrombus formation in COVID-19 may involve the venous and arterial vasculature. As thrombotic complications of infectious respiratory diseases are increasingly considered in the context of COVID-19, the fact that thrombosis in lung diseases of viral and bacterial etiology was described long before the pandemic is overlooked. Pre-pandemic studies show that bacterial and viral respiratory infections are associated with an increased risk of thrombotic complications such as myocardial infarction, ischemic stroke, pulmonary embolism, and other critical illnesses caused by arterial and venous thrombosis. This narrative review article aims to summarize the current evidence regarding thrombotic complications and their pathogenesis in acute lower respiratory tract infections.

The Recent Increase in Invasive Bacterial Infections: A Report From the National COVID Cohort Collaborative

Background: When coronavirus disease 2019 (COVID-19) mitigation efforts waned, viral respiratory infections (VRIs) surged, potentially increasing the risk of postviral invasive bacterial infections (IBIs). We sought to evaluate the change in epidemiology and relationships between specific VRIs and IBIs [complicated pneumonia, complicated sinusitis and invasive group A streptococcus (iGAS)] over time using the National COVID Cohort Collaborative (N3C) dataset. Methods: We performed a secondary analysis of all prospectively collected pediatric (<19 years old) and adult encounters at 58 N3C institutions, stratified by era: pre-pandemic (January 1, 2018, to February 28, 2020) versus pandemic (March 1, 2020, to June 1, 2023). We compared the characteristics and outcomes of patients with prespecified VRIs and IBIs, including correlation between VRI cases and subsequent IBI cases. Results: We identified 965,777 pediatric and 9,336,737 adult hospitalizations. Compared with pre-pandemic, pandemic-era children demonstrated higher mean monthly cases of adenovirus (121 vs. 79.1), iGAS (5.8 vs. 3.3), complicated pneumonia (282 vs. 178) and complicated sinusitis (29.8 vs. 16.3), P < 0.005 for all. Among pandemic-era children, peak correlation between RSV cases and subsequent complicated sinusitis cases occurred with a 60-day lag (correlation coefficient 0.56, 95% confidence interval: 0.52–0.59, P < 0.001) while peak correlation between influenza and complicated sinusitis occurred with a 33-day lag (0.55, 0.51–0.58, P < 0.001). Correlation among other VRI–IBI pairs was modest during the pandemic and often lower than during the pre-pandemic era. Conclusions: Since COVID-19 emerged, mean monthly cases of iGAS, complicated pneumonia, and complicated sinusitis have been higher. Pandemic-era RSV and influenza cases were correlated with subsequent cases of complicated sinusitis in children. However, many other VRI–IBI correlations decreased during the pandemic.

The potential of HBV cure: an overview of CRISPR-mediated HBV gene disruption

Hepatitis B virus (HBV) infection is a common cause of liver disease worldwide. The current antiviral treatment using nucleotide analogues (NAs) can only suppress de novo HBV replication but cannot eliminate chronic HBV infection due to the persistence of covalently closed circular (ccc) DNA that sustains viral replication. The CRISPR/Cas9 system is a novel genome-editing tool that enables precise gene disruption and inactivation. With high efficiency and simplicity, the CRISPR/Cas9 system has been utilized in multiple studies to disrupt the HBV genome specifically, eliciting varying anti-HBV effects both in vitro and in vivo. Additionally, multi-locus gene targeting has shown enhanced antiviral activity, paving the way for combination therapy to disrupt and inactivate HBV cccDNA as well as integrated HBV DNA. Despite its promising antiviral effects, this technology faces several challenges that need to be overcome before its clinical application, i.e., off-target effects and in vivo drug delivery. As such, there is a need for improvement in CRISPR/Cas9 efficiency, specificity, versatility, and delivery. Here, we critically review the recent literature describing the tools employed in designing guide RNAs (gRNAs) targeting HBV genomes, the vehicles used for expressing and delivering CRISPR/Cas9 components, the models used for evaluating CRISPR-mediated HBV gene disruption, the methods used for assessing antiviral and off-target effects induced by CRISPR/Cas9-mediated HBV gene disruption, and the prospects of future directions and challenges in leveraging this HBV gene-editing approach, to advance the HBV treatment toward a clinical cure.

Hepatitis Delta Coinfection Rates and All-Cause Mortality Among Hepatitis B-Infected Veterans in the USA.

Screening for hepatitis D virus (HDV) is recommended for all individuals with hepatitis B virus (HBV) infection. Coinfected individuals experience more severe liver-related outcomes. We determined the HDV testing and coinfection rates and all-cause mortality among those infected with HBV. We used the US Department of Veterans Affairs (VA) healthcare system's national databases to identify individuals with HBV infection. We determined the proportion of individuals referred to gastroenterologists/hepatologists, or infectious diseases providers, and the proportion screened and tested positive for HDV. We calculated the HBV treatment rates, defined as ≥ 3 months of continuous prescription with an approved drug. Finally, we calculated all-cause mortality stratified by HDV coinfection and HBV treatment status. Among 44,951 individuals with at least one positive HBsAg, HBeAg or HBV DNA test, 5964 (13.3%) were screened for HDV (180 [3.0%] tested positive), and 28,291 (62.9%) were referred to gastroenterology/hepatology or infectious diseases. Treatment for HBV was prescribed for 73 (40.5%) of HDV-coinfected and 2425 (41.9%) HDV-uninfected individuals. All-cause mortality rate per 100 person-years was lower among those without HDV coinfection (2.98 for untreated HBV, 2.53 for treated HBV; p < 0.001) compared with those with HDV coinfection (5.14 for untreated HBV, 3.0 for treated HBV; p = 0.02). Kaplan-Meier curves demonstrated a significantly higher mortality among HDV-coinfected individuals who were not treated for HBV (log-rank p < 0.0001). Screening rates for HDV among HBV-infected individuals are suboptimal. While HDV coinfection is associated with higher all-cause mortality, HBV treatment may confer a survival benefit.

Dengue Envelope Protein as a Cytotoxic Factor Inducing Hemorrhage and Endothelial Cell Death in Mice

Dengue virus (DENV) infection, prevalent in tropical and subtropical regions, can progress to dengue hemorrhagic fever (DHF), which increases mortality during secondary infections. DHF is characterized by endothelial damage and vascular leakage. Despite its severity, no specific antiviral treatments exist, and the viral factors responsible for endothelial damage remain unclear. This study examines the role of the DENV envelope protein domain III (EIII) in inducing endothelial apoptosis using a mouse model. Additionally, we aim to explore whether cell death-inducing pathways could serve as drug targets to ameliorate EIII-induced endothelial injury and hemorrhage. In vitro experiments using human endothelial HMEC-1 cells demonstrated that both recombinant EIII (rEIII) and DENV markedly induced caspase-3-mediated endothelial cell death, an effect that was attenuated by co-treatment with chondroitin sulfate B (CSB), N-acetyl cysteine (NAC), and the caspase-3 inhibitor z-DEVD-FMK. In vivo, sequential injections of rEIII and anti-platelet immunoglobulin in mice, designed to mimic the clinical phase of DHF with peak viremia followed by an increase in DENV-induced Ig, including autoantibodies, revealed that these dual treatments markedly triggered caspase-3-dependent apoptosis in vascular endothelial cells at hemorrhage sites. Treatments with z-DEVD-FMK effectively reduced DHF-like symptoms such as thrombocytopenia, hemorrhage, inflammation, hypercoagulation, and endothelial damage. Additionally, CSB and NAC alleviated hemorrhagic symptoms in the mice. These results suggest that targeting EIII, reactive oxygen species, and caspase-3-mediated apoptosis could offer potential therapeutic strategies for addressing EIII-induced hemorrhagic pathogenesis.

The Association of IFNL4 Gene Polymorphisms with Hepatitis B Virus (HBV) Infection in the Northern Region of Pará, Brazil

It is heavily suggested that one IFNL4 gene polymorphism, rs12979860 (T/C), exerts influence on the outcome of HBV infection, with the rs12979860-T allele being classified as a risk predictor, and the rs12979860-C allele being classified as a protective one. This study investigated whether the rs12979860 IFNL4 gene polymorphism presented any association with the clinical severity for HBV carriers in an admixed population in Northern Brazil. A total of 69 samples were investigated from infected people from the city of Belém-Pará. The rs12979860-T allele was positively associated with HBV infection, suggesting a higher risk of chronicity. This research’s importance is that the polymorphism influence was investigated in a population of HBV carriers with a heterogeneous genetic profile, formed through the extensive admixture of different ethnic groups, including Europeans, Africans, and Natives with indigenous heritage. This analysis is particularly important since highly mixed populations do not always follow the same association patterns previously established by studies using populations classified as more genetically homogeneous, due to a different formation process.

A Programme of Hepatitis C Surveillance With Active Linkage to Care (HEAL) for Inpatients in Two Tertiary Hospitals in Jiangsu, China.

Hepatitis C virus (HCV) infection is a major public health burden in China, affecting more than 10 million individuals. We aimed to evaluate the effectiveness of a hospital-based intervention programme for HCV Surveillance with linkage to care (HEAL) in a prospective cohort. The HEAL programme was carried out targeting inpatients from non-infectious departments of two tertiary hospitals in Jiangsu, China. It consisted of an educational campaign to raise awareness of physicians from non-IDs to promote HCV surveillance, a patient-navigator-centred clinical algorithm responsible for the efficient follow-up of patients with positive HCV antibody, including comprehensive testing, diagnosis and treatment. We characterised the rate of linkage to HCV diagnosis, care and treatment during the pre-intervention period (from 1 July 2016 and June 30, 2018) and after the intervention (from March 2019 to May 2021). During the pre-intervention period, 89,303 (45.3%) out of 196,780 non-ID inpatients were screened for anti-HCV, and 631 patients were tested positive. One hundred and fifty-six (24.7%) patients was followed up for HCV RNA confirmatory testing, and 58 (37.1%) of patients further were diagnosed with chronic HCV infection (CHC). Only 18 (31.3%) of the diagnosed patients with CHC were linked to hepatitis C clinics for treatment, 10 (55.6%) patients received antiviral regimen. Among them, two (11.1%) received DAA treatment, while eight (44.4%) adopted peginterferon/ribavirin regimen. During the intervention period, 232,275 patients were hospitalised in non-infectious department and 151,203 (65.1%) were screened for anti-HCV. Of these, 960 patients tested positive for HCV antibodies, resulting in a prevalence of anti-HCV positivity of 0.63%. Six hundred and seventy (69.8%) patients were enrolled, and 100% were followed up for HCV RNA confirmatory testing. Two hundred and ninety-one (43.4%) individuals with active HCV were identified. Two hundred and thirty-eight (81.8%) of HCV-infected individuals were linked to HCV care, and 157 (65.9%) were linked to treatment. Compared to the pre-intervention period, there was a 2.61-fold increase in the percentage of patients linked to care and a 5.94-fold increase in the proportion of patients who started DAAs therapy. This HEAL programme achieved enhanced HCV Surveillance with linkage to care, which has been demonstrated as an effective strategy in the hospital setting to improve the hepatitis C care continuum by identifying inpatients unaware of their HCV status and facilitating their access to HCV treatment.

To Evaluate The Histomorphological Changes Of Postmortem Transthoracic Needle Biopsy/Autopsy Lung In COVID-19 Patients

Objective: To study the histomorphological changes in postmortem needle biopsy/autopsy lung in COVID-19 Patients. Study Design: This was an observational study done at Shri Atal Bihari Vajpayee Medical College &amp; Research Institute, Bengaluru, and Karnataka from March 2021 to May 2021. Methodology: A total of 30 patients who died of Covid-19 were included and all of them were diagnosed to be Covid -19 positive by RT-PCR testing. Post-mortem transthoracic needle biopsy was done to obtain lung tissue by using B-Bard biopsy gun in midaxillary approach. The biopsy samples were grossed and processed after fixing for 48hrs. The slides obtained were stained by routine hematoxylin and eosin stain, studied for morphology of the lung tissue and findings were recorded. Results: We obtained consent for post-mortem transthoracic needle biopsy/autopsy of lung in 30 deceased cases. All these cases were positive for SARS –COV2 on RT-PCR. The age of the cases was ranging from 26-72 years and median age is 53years, males (63.3%) were affected more than females (36.7%). Most deceased had comorbidities, among them diabetes mellitus (26.6%) and hypertension (26.6%) were most common. Lung biopsy samples were taken from 30 deceased patients. Histomorphological feature of diffuse alveolar damage was seen in 90% (27 out of 30) cases. Other findings noted on microscopy were chronic interstitial inflammation in 6.7% cases, pulmonary edema (3.33%), intra alveolar haemorrhage (3.33%) and viral cytopathic changes (3.33%). Conclusion: This study highlighted the pulmonary morphological changes which are most prominent in COVID-19 infections, but it was a difficult to ascertain that the findings are related to viral infection or due to associated coomorbidities

Activation of PKR by a short-hairpin RNA

Recognition of viral infection often relies on the detection of double-stranded RNA (dsRNA), a process that is conserved in many different organisms. In mammals, proteins such as MDA5, RIG-I, OAS, and PKR detect viral dsRNA, but struggle to differentiate between viral and endogenous dsRNA. This study investigates an shRNA targeting DDX54’s potential to activate PKR, a key player in the immune response to dsRNA. Knockdown of DDX54 by a specific shRNA induced robust PKR activation in human cells, even when DDX54 is overexpressed, suggesting an off-target mechanism. Activation of PKR by the shRNA was enhanced by knockdown of ADAR1, a dsRNA binding protein that suppresses PKR activation, indicating a dsRNA-mediated mechanism. In vitro assays confirmed direct PKR activation by the shRNA. These findings emphasize the need for rigorous controls and alternative methods to validate gene function and minimize unintended immune pathway activation.

Ruhao Dashi granules exert therapeutic effects on H1N1 influenza virus infection by altering intestinal microflora composition

ObjectiveAntiviral medications for influenza could be ineffective due to the emergence of resistant influenza virus strains. Ruhao Dashi (RHDS) granules possess anti-inflammatory and antibacterial effects. The present study aimed to determine the efficacy of RHDS granules in treating influenza-infected mice and the mechanism underlying this treatment as well as its effect on the intestinal flora composition of the infected mice.MethodsThe HPLC-UV method was used to identify the active components of RHDS granules. ICR mice were infected with influenza A virus (IAV) H1N1 subtype through a nasal drip. After the influenza mice model was successfully established, the pathological changes in the lungs were observed for 5 days after gavage treatment with 0.9% sterile saline and low, medium, and high doses (0.07, 0.14, and 0.28 g/mL, respectively) of RHDS granules. The serum levels of the cytokines IL-6 and TNF-α and sIgA were detected by ELISA. Real-time fluorescence quantitative PCR and western blotting assay were performed to determine the expression levels of the tight junction (TJ) proteins claudin-1, occludin, and zonula occludens-1 (ZO-1) in colon tissues. Furthermore, 16S rRNA gene sequencing of feces samples was conducted to assess the effect of RHDS granules on the gut microbiota.ResultsRHDS granules exerted a protective effect on the lung tissues of IAV-infected mice; moreover, the granules reduced the synthesis of proinflammatory cytokines and increased the relative expression levels of claudin-1, occludin, and ZO-1 in colon tissues. Furthermore, RHDS granule treatment increased the relative abundance of Lactobacillus, Akkermansia, and Faecalibaculum and decreased the relative abundance of Muribaculaceae; thus, RHDS granules could stabilize the intestinal microbiota to some extent.ConclusionRHDS granules exert a therapeutic effect on IAV-infected mice probably by modifying the structural composition of their intestinal microbiota.

Evaluation and control strategy analysis of influenza cases in Jiujiang City, Jiangxi Province, China from 2018 to 2022.

According to World Trade Organization (WTO) statistics, the incidence of seasonal influenza in China has been on the rise since 2018. The aim of this study was to identify and investigate the influence of factors related to the incidence of four common types of influenza viruses. Data of patients with common cold and associated virus infections are described, and a logistic regression model based on gender, age and season was established. The relationship between virus type and the above three factors was analyzed in depth and significant (p<0.05) associations noted. We noted a fluctuation trend, with the infection rate of influenza virus showing an upward trend from 2018 to 2019 and from 2021 to 2022 and a downward trend from 2019 to 2021. The total number of cases in adolescents aged 18-30 years was higher than that in the elderly. The impact of different types of influenza virus on the population ranked from large to small, with special roles played by Influenza B/Victoria, H3N2, Influenza A/H1N1 pdm and Influenza B/Yamagata.

Picornavirus Evolution: Genomes Encoding Multiple 2ANPGP Sequences—Biomedical and Biotechnological Utility

Alignment of picornavirus proteinase/polymerase sequences reveals this family evolved into five ‘supergroups’. Interestingly, the nature of the 2A region of the picornavirus polyprotein is highly correlated with this phylogeny. Viruses within supergroup 4, the Paavivirinae, have complex 2A regions with many viruses encoding multiple 2ANPGP sequences. In vitro transcription/translation analyses of a synthetic polyprotein comprising green fluorescent protein (GFP) linked to β-glucuronidase (GUS) via individual 2ANPGPs showed two main phenotypes: highly active 2ANPGP sequences—similar to foot-and-mouth disease virus 2ANPGP—and, surprisingly, a novel phenotype of some 2ANPGP sequences which apparently terminate translation at the C-terminus of 2ANPGP without detectable re-initiation of downstream sequences (GUS). Probing databases with the short sequences between 2ANPGPs did not reveal any potential ‘accessory’ functions. The novel, highly active, 2A-like sequences we identified substantially expand the toolbox for biomedical/biotechnological co-expression applications.