Intervirology最新文献

Introduction: Chronic hepatitis C infection can result in insulin resistance (IR). We have previously shown that it occurs through the interaction of pathways for glucose homeostasis, insulin signaling, and autophagy. But it is not known how soon the pathways are activated and how IR is related to the signals generated by catabolic and anabolic conditions occurring in infected cells. We have extended our studies to a cell culture system mimicking acute infection and to downstream pathways involving energy-sensor AMPK and nutrient-sensor mTOR that are active in catabolic and anabolic processes within the infected cells.

Methods: Huh7 liver cells in culture were infected with hepatitis C virus (HCV). We performed proteomics analysis of key proteins in infected cells by Western blotting and IP experiments, with or without IFNα exposure as a component of conventional therapeutic strategy.

Results: We present evidence that (a) IRS-1 Ser312, Beclin-1, protein conjugate Atg12-Atg5 or GS Ser641 are up-regulated early in infection presumably by activating the same pathways as utilized for persistent infection; (b) Bcl-XL, an inhibitor of both autophagy and apoptosis, is present in a core complex with IRS-1 Ser312 and Beclin-1 during progression of IR; (c) AMPK level remains about the same in infected cells where it is activated by phosphorylation at Thr172 concomitant with increased autophagy, a hallmark of catabolic conditions; (d) an mTOR level that promotes anabolism is increased rather than decreased under an expanded autophagy; (e) hypophosphorylation of translational repressor 4E-BP1 downstream of mTOR is suggestive of reduced protein synthesis; and (f) β-catenin, is up-regulated but not phosphorylated suggesting indirectly our previous contention that its kinase, GSK-3β, is mostly in an inactive state.

Conclusion: We report that in the development of IR following chronic infection, anabolic and catabolic pathways are activated early, and the metabolic interaction occurs possibly in a core complex with IRS-1 Ser312, Beclin-1, and autophagy inhibitor Bcl-XL. Induction of autophagy is usually controlled by a two-edged mechanism acting in opposition under anabolic and catabolic conditions by AMPK/mTOR/4E-BP1 pathway with GSK-3β-mediated feedback loops. However, we have observed an up-regulation of mTOR along with an up-regulation of AMPK caused by HCV infection is a deviation from the normal scenario described above which might be of therapeutic interest.

Introduction: The effect of maltodextrin-based nanoparticles with an anionic phospholipid core (lipid-based nanoparticles [NPLs]) on the infection of a human tumoral cell line with poliovirus (PV) has been studied.

Methods: NPLs were synthesized and associated with the PV type 1 Sabin strain, and the formulations were characterized. PV and PV/NPL formulations were inoculated to HEp-2 cells.

Results: The surface charge and the diameter of PV/NPL formulation suggest that viral particles were adsorbed onto NPLs. When HEp-2 cells were inoculated with 1 tissue culture 50% infectious dose/mL PV associated with NPLs, the cytopathic effect appeared obvious; the levels of the infectious titer of culture supernatants and the proportion of VP1-positive cells were higher. The level of intracellular viral RNA extracted from HEp-2 cells inoculated with PV/NPL formulation was higher as well.

Conclusion: These results show that NPLs can enhance the infection with a virus and suggest that they might be used in virotherapy to increase the virus-mediated lysis of tumor cells.

Introduction: Diarrheal diseases constitute a significant public health problem in terms of mortality and morbidity. In Honduras and around the world, RVs have consistently emerged as the single most important etiologic agent in acute childhood diarrhea. However, other viruses, such as NoVs and HAstVs, have also been shown to be responsible for viral gastroenteritis. Unfortunately, the country has limited information concerning the etiologic role of these viral agents in acute gastroenteritis. This study investigated the frequency, genotypes, and epidemiological characteristics of RV-A, NoVs, and HAstVs among children under 5 years old in Distrito Central, Honduras.

Methods: Stool samples and their corresponding epidemiological data were collected from children with acute gastroenteritis in three healthcare centers in Distrito Central. All samples were screened by immunoassays for RV-A and HAstVs. RV-A-positive samples were molecularly characterized by RT-PCR and genotyping assays. RT-PCR was also applied to confirm HAstVs positivity and to detect NoVs, followed by nucleotide sequencing to assign their genotypes.

Results: Our results show that at least one viral agent was detected in 31% of the children. The frequency of RV-A, NoVs, and HAstVs was 14%, 13%, and 5%, respectively. The most frequent RV-A genotype was G2P[4], occurring in 93% of cases. 92.3% of NoVs-positive samples belonged to genogroup II, with GII.4 and GII.16 being the most common. HAstVs were clustered into three genotypes: HAstV-1, HAstV-2, and HAstV-8. Only one sample showed coinfection with NoVs and HAstVs.

Conclusion: This comprehensive molecular and epidemiological characterization of enteric viruses demonstrates the vast diversity of these agents and describes for the first time NoVs and HAstVs as causative agents of acute childhood gastroenteritis in Distrito Central, Honduras. This suggests that further in-depth studies of the pediatric population are necessary to develop and implement effective preventive and control measures in the country.

Introduction: Molnupiravir is one of the oral direct-acting antivirals against SARS-CoV-2, largely deployed during the COVID-19 pandemic since the 2022 Omicron wave. While efficacy has been questioned in post-marketing clinical trials (leading to the EMA withdrawing its authorization), growing concerns have mounted regarding its possible mutagenic effects on the virus. While it has been assumed that either all the host viral load was cleared by the drug or drug-generated variants were not fit enough to survive, several lineages with a high transition/transversion ratio (a signature of molnupiravir action) have been recently reported from GISAID.

Methods: We report here a systematic analysis of the GISAID database for sequences showing a molnupiravir signature, exposing a public web-based interface (https://ukcovid.xyz/molnupiravir/), and performing an imputation analysis based on per-country prescription (corrected by sequencing).

Results: Our analysis confirms a direct correlation between the number of molnupiravir courses and the number of mutationally signed sequences deposited in GISAID in individual countries.

Conclusions: Molnupiravir can generate fit SARS-CoV-2 variants that transmit in the general population.

Introduction: Chrysophanol (Cho) is a natural anthraquinone with biological effects such as inducing ferroptosis and anticancer activity. The hepatitis B virus X protein (HBx) is essential for HBV replication. We aimed to identify the key pathways in HBx-induced hepatic stellate cell (HSC) activation and to characterize the potential mechanisms of action of Cho against liver fibrosis.

Methods: HSC-T6 cells were transfected with FLAG (control group) or FLAG-HBx (HBx group), and RNA sequencing and Western blotting analysis were conducted to assess the effects of HBx and Cho on specific molecular targets and signaling pathways.

Results: Gene ontology and pathway analyses indicated that the genes targeted by HBx participate in immunological responses, chemokine and cytokine activity, cell-substrate adhesion, extracellular matrix organization, growth factor binding, defense responses, and antigen processing and presentation. RNA-seq and Western blotting data revealed that HBx-activated HSC-T6 cells exhibited upregulated expression of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), S6, phosphorylated S6 (p-S6), peroxisome proliferator-activated receptor (PPAR-α), phosphorylated-PPAR-α (p-PPAR-α), CYP27, α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and Integrin-β1, which was reversed after treatment with Cho. These results were also verified in a HBx-activated HSC-T6 and LX-2 cell model and thioacetamide-induced liver fibrosis mouse model.

Conclusions: Thus, our findings indicate that Cho ameliorates HBx-induced HSC activation and liver fibrosis via inhibition of the mTOR and PPARs signaling pathways, suggesting that Cho is a potential therapeutic for chronic liver inflammation-mediated diseases.

Background: The world has witnessed one of the largest pandemics, dubbed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of December 2020, the USA alone reported 98,948 cases of coronavirus disease 2019 (COVID-19) infection during pregnancy, with 109 related maternal deaths. Current evidence suggests that unvaccinated pregnant women infected with SARS-CoV-2 are at a higher risk of experiencing complications related to COVID-19 compared to nonpregnant women. This review aimed to provide healthcare workers and non-healthcare workers with a comprehensive overview of the available information regarding the efficacy of vaccines in pregnant women.

Summary: We performed a systematic review and meta-analysis following PRISMA guidelines. The search through the database for articles published between December 2019 and October 2021 was performed. A comprehensive search was performed in PubMed, Scopus, and EMBASE databases for research publications published between December 2019 and October 2021. We focused on original research, case reports, case series, and vaccination side effect by authoritative health institutions. Phrases used for the Medical Subject Heading [MeSH] search included ("COVID-19" [MeSH]) or ("Vaccine" [MeSH]) and ("mRNA" [MeSH]) and ("Pregnant" [MeSH]). Eleven studies were selected and included, with a total of 46,264 pregnancies that were vaccinated with mRNA-containing lipid nanoparticle vaccine from Pfizer/BioNTech and Moderna during pregnancy. There were no randomized trials, and all studies were observational (prospective, retrospective, and cross-sectional). The mean maternal age was 32.2 years, and 98.7% of pregnant women received the Pfizer COVID-19 vaccination. The local and systemic adverse effects of the vaccination in pregnant women were analyzed and reported. The local adverse effects of the vaccination (at least 1 dose) such as local pain, swelling, and redness were reported in 32%, 5%, and 1%, respectively. The systemic adverse effects such as fatigue, headaches, new onset or worsening of muscle pain, chills, fever, and joint pains were also reported in 25%, 19%, 18%, 12%, 11%, and 8%, respectively. The average birthweight was 3,452 g. Among these pregnancies, 0.03% were stillbirth and 3.68% preterm (<37 weeks) births.

Key messages: The systemic side effect profile after administering the COVID-19 mRNA vaccine to pregnant women was similar to that in nonpregnant women. Maternal and fetal morbidity and mortality were lowered with the administration of either one or both the doses of the mRNA COVID-19 vaccination.

Introduction: Acute hemorrhagic conjunctivitis (AHC) outbreaks are caused mostly by viruses. During July-August 2023, there was a sudden spike in acute hemorrhage conjunctivitis cases in Eastern Uttar Pradesh, India. To identify the etiological and gain molecular epidemiology of the agent, the study was conducted.

Methodology: Conjunctival swabs were collected from patients (n = 128) with presumed acute hemorrhage conjunctivitis visiting two tertiary care hospitals.

Results: Enteroviruses infection was identified in 96 (75%) patients. In these patients, coxsackievirus A24 (CV-A24) infection was further confirmed by targeting the genetic regions of 3C protease and VP1. Furthermore, the study established the outbreak was caused by the genotype IV of CV-A24 with the highest genetic similarity with CV-A24 reported from Northeast India, China, and Pakistan circulating during the same period. The comparison of our study sequences with earlier Indian outbreak strains (2007) revealed four amino acid substitutions at the 3C region ("S21N," "V30I," "S66I," and "V75I") and three non-synonymous mutations at the VP1 region ("L16I," "P21S," and "N301D").

Conclusion: The study findings revealed that the AHC outbreak was caused by genotype IV of CV-A24 in this region. Molecular identification accompanied by phylogenetic analysis will be useful in studying the enterovirus epidemiology associated with AHC outbreaks.

Introduction: Cervical cancer (CC) is a prevailing malignant tumor in women, mainly caused by human papillomavirus (HPV) infection. This study investigated miR-106a expression in the serum of HPV-positive CC patients and estimated its value in diagnosis and prognosis.

Methods: We enrolled 120 CC patients as study subjects, with another 80 healthy women as controls. Clinical baseline data and clinicopathological indexes including age, tumor size, differentiation degree, FIGO stage, lymph node metastasis, and squamous cell carcinoma antigen (SCC-Ag) were recorded. Serum miR-106a expression was measured using reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve was employed to estimate the efficacy of miR-106a in diagnosing CC or HPV-positive CC. Under a 5-year follow-up, patient survival was recorded, and the impact of miR-106a on overall survival rate was analyzed by the Kaplan-Meier method. The logistic regression model was used to analyze whether miR-106a was an independent prognostic factor for HPV infection in CC patients.

Results: Serum miR-106a was upregulated in CC patients and the level >1.365 assisted the CC diagnosis. miR-106a expression in HPV-positive CC patients was elevated relative to HPV-negative CC patients, and serum miR-106a level >1.300 distinguishing HPV positive and HPV negative. HPV positivity was linked with tumor differentiation degree, FIGO stage, lymph node metastasis, and SCC-Ag in CC patients, but not with age and tumor size. High expression of miR-106a in HPV-positive CC patients increased the risk of poor prognosis, and miR-106a expression is an independent prognostic factor for HPV infection in CC patients.

Conclusion: High expression of miR-106a assists in the diagnosis of HPV-positive CC and predicts poor prognosis.

Introduction: MicroRNAs, or miRNAs, with regulatory performance in inflammatory responses and infection are the prevalent manifestations of severe coronavirus disease (COVID-19). This study aimed to evaluate whether PBMC miRNAs are diagnostic biomarkers to screen the ICU COVID-19 and diabetic COVID-19 subjects.

Methods: Candidate miRNAs were selected through previous studies, and then the PBMC levels of selected miRNAs (miR-28, miR-31, miR-34a, and miR-181a) were measured via quantitative reverse transcription PCR. The diagnostic value of miRNAs was determined by the receiver operating characteristic (ROC) curve. The bioinformatics analysis was utilized to predict the DEM genes and relevant bio-functions.

Results: The COVID-19 patients admitted to ICU had significantly greater levels of selected miRNAs compared to non-hospitalized COVID-19 and healthy people. Besides, the mean miR-28 and miR-34a expression levels in the diabetic COVID-19 group were significantly upregulated when compared with the non-diabetic COVID-19 group. ROC analyses demonstrated the role of miR-28, miR-34a, and miR-181a as new biomarkers to discriminate the non-hospitalized COVID-19 group from the COVID-19 patients admitted to ICU samples, and also miR-34a can probably act as a useful biomarker for screening diabetic COVID-19 patients. Using bioinformatics analyses, we found the performance of target transcripts in many bioprocesses and diverse metabolic routes such as the regulation of multiple inflammatory parameters.

Discussion: The difference in miRNA expression patterns between the studied groups suggested that miR-28, miR-34a, and miR-181a could be helpful as potent biomarkers for diagnosing and controlling COVID-19.

Background: Emerging virus infections provoke health problems in people and animals, which generate social and economic issues worldwide. This has spurred the search for new pharmacological strategies to confront them.

Summary: The purpose of this review is to draw the reader's attention to pharmacological evaluations of glycyrrhizic acid (GA) and its analogs on the broad range of viruses known in human and veterinary medicine. GA is the main water-soluble constituent extracted from the roots of plants from the genus Glycyrrhiza, commonly known as licorice root. It has long been used due to its broad spectrum of bioactivities, including anti-inflammatory, antiulcer, and antitumor properties. It has also been proposed as an antiviral agent. Medicines derived from GA are currently being used to combat acute and chronic hepatitis and herpes viruses.

Key messages: This review suggests that GA could be a new broad-spectrum antiviral due to its ability to inhibit DNA or RNA viruses both in vitro and in vivo. GA could be a potential drug for preventing and/or treating various viral diseases.