Virology Journal最新文献

Porcine Reproductive and Respiratory Syndrome (PRRS) causes huge economic losses to pig farms worldwide. Currently available vaccines do not always offer complete protection, due to the extreme variability of the virus. Therefore, good farming practices must be improved to prevent the disease from spreading across the pig production system. In this study, we inferred the dynamics of PRRSV population in Italy by applying bayesian methods on our ORF7 sequence dataset collected during a 15-years period. Random subsets from the overall dataset were built to reduce analysis runtime. Calculated evolutionary rate was consistent between subsets and with other findings on PRRSV and other RNA viruses (4-7 × 10^- 3 substitution/site/year) while Time to the Most Recent Common Ancestor was less consistent (from 1980 to 1990). Despite this, in all population dynamic reconstructions, a massive increase in size calculated in early 2000s lasting until around 2010 was inferred. This spike is followed by very heterogeneous dynamics with some differences between subsets, probably due to the random sampling. Geographical origin was inferred in Emilia-Romagna region despite Lombardy being the region with the highest number of farmed animals and farm size. These findings reflect the choices regarding farm management and biosecurity taken in the last two decades, and not strictly related to PRRS. Phylogeny and phylogeography are powerful tools to better understand microorganisms population dynamics and make appropriate choices for disease control.

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has profoundly impacted global healthcare systems and spurred extensive research efforts over the past three years. One critical aspect of the disease is the intricate interplay between the virus and the host immune response, particularly the role of inflammatory gene expression in severe COVID-19. While numerous previous studies have explored the role of genetic polymorphisms in COVID-19, research specifically focusing on inflammatory genes and their associations with disease severity remains limited. This review explores the relationship between severe COVID-19 outcomes and genetic polymorphisms within key inflammatory genes. By investigating the impact of genetic variations on immune responses, which include cytokine production and downstream signalling pathways, we aim to provide a comprehensive overview of how genetic polymorphisms contribute to the variability in disease presentation. Through an in-depth analysis of existing literature, we shed light on potential therapeutic targets and personalized approaches that may enhance our understanding of disease pathogenesis and treatment strategies.

Jingmen tick virus (JMTV) is a novel segmented Flavivirus that was first identified from Rhipicephalus microplus in the Jingmen region of Hubei Province, China, in 2010. Subsequently, it was detected in a variety of countries and regions around the world. Meanwhile, JMTV has been proved to be pathogenic to humans and animals and could cause viremia in animals. However, the pathogenic mechanism of JMTV and what role animals play in the viral cycle have not yet been elucidated. In this study, 38 sheep sera were collected from Xinyang region of Henan Province, China and 204 ticks attached to the sheep were collected. The qRT-PCR and nested PCR were used to confirm the presence of JMTV in serum and tick samples. The results showed that the positive rate of JMTV in serum and ticks was 13.16% (5/38) and 7.84% (16/204), respectively. Phylogenetic analysis showed that JMTV sequences in sheep and ticks shared a high degree of identity with each other, and JMTV was relatively conserved in evolution. These results enriched the evidence for the prevalence of JMTV in animals and further deepened our understanding of the mechanisms and routes of JMTV transmission.

In preclinical studies, GST-HG141, a novel hepatitis B virus (HBV) capsid assembly modulator displayed potent anti-HBV activity in vitro and strong efficacy in HBV animal models. A randomized, double-blind, ascending phase 1b trial assessed the pharmacokinetics, safety, and efficacy of GST-HG141 in chronic hepatitis B (CHB) individuals. Thirty treatment-naïve CHB patients were enrolled in three cohorts (25, 50, and 100 mg twice orally after meals daily) over 28 days, with 10 subjects per cohort (8:2 ratio for GST-HG141 and placebo). Dose-related safety and tolerability, pharmacokinetic profiles, and drug responses were evaluated. GST-HG141 exhibited a generally favorable safety profile across all doses with predominantly mild adverse reactions, including three cases of grade 1 transaminase elevations. Significant reductions in HBV DNA and pregenomic RNA (pgRNA) levels were observed across all doses of (25, 50, and 100 mg of GST-HG141, twice-daily) after 28 days of treatment. Pharmacokinetic analysis showed a consistent linear trend in GST-HG141 concentrations, with mean trough concentrations ranging from 75 to 240 ng/mL. These concentrations adequately covered the protein binding-adjusted EC50 (16.89 ng/mL) by factors of 4.4, 11.1, and 14.6 for doses of 25, 50, and 100 mg, respectively. Our study demonstrated GST-HG141's well-tolerated profile up to 100 mg over 4 weeks, alongside robust antiviral activity in CHB patients, supporting its progression into further clinical investigation for CHB management.

Background: The global prevalence of metabolic syndrome (MetS) in people living with HIV (PLWH) is on the rise in the post era of antiretroviral therapy (ART). Nevertheless, there are no validated predictive models available for assessing the risk of MetS in this specific population.

Methods: This study included PLWH who participated in annual follow-ups at Southern Medical University Nanfang Hospital from September 2022 to November 2023. Participants enrolled in this study were divided into the training set and validation set based on the follow-up duration. We employed both multivariate logistic regression and lasso regression to develop three distinct prediction models. Subsequently, the optimal model was determined through comprehensive analyses, including receiver operating characteristic (ROC) curve analysis, calibration curve, and decision curve analysis (DCA). Ultimately, we generated a nomogram for the optimal model and analyzed the correlation between the model score and the components of MetS.

Results: A total of 1017 participants were included in this study, with 814 in the training set and 203 in the validation set. The ultimate prediction model of MetS risk in PLWH incorporated five factors: age, CD8 + T cell counts, controlled attenuation parameter (CAP), gamma-glutamyl transferase (γ-GT) and lactate dehydrogenase (LDH). The area under the ROC curve (AUC) of the model in the training set and validation set was 0.849 and 0.834, respectively. Furthermore, we revealed a significant correlation between the model score and the MetS components. Additionally, the model score revealed significant group differences in MetS and related metabolic disorders.

Conclusions: This study established a potential model for predicting MetS in PLWH.

Background: Duck circovirus (DuCV) infections commonly induce immunosuppression and secondary infections in ducks, resulting in significant economic losses in the duck breeding industry. Currently, effective vaccines and treatments for DuCV have been lacking. Therefore, rapid, specific, and sensitive detection methods are crucial for preventing and controlling DuCV.

Methods: A lateral flow strip (LFS) detection method was developed using recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 12a (Cas12a). The RPA-CRISPR/Cas12a-LFS targeted the DuCV replication protein (Rep) and was operated at 37 ℃ and allowed for visual interpretation without requiring sophisticated equipment.

Results: The results revealed that the reaction time of RPA-CRISPR/Cas12a-LFS is only 45 min. This method achieved a low detection limit of 2.6 gene copies. Importantly, this method demonstrated high specificity and no cross-reactivity with six other avian viruses. In a study involving 97 waterfowl samples, the Rep RPA-CRISPR/Cas12a-LFS showed 100% consistency and agreement with real-time quantitative polymerase chain reaction.

Conclusion: These findings underscored the potential of this user-friendly, rapid, sensitive, and accurate detection method for on-site DuCV detection.

Herpes simplex virus type 1 (HSV-1) is the leading pathogen in the maxillo-facial region, affecting millions of individuals worldwide. Its periodic reactivation aligns with the most common course pattern of periodontal disease. The present study used RNA sequencing to investigate the transcriptomes of human gingival fibroblasts (HGFs) following HSV-1 infection from the early to late stages (12-72 h). At the early stage of infection (12 h post-infection), the most upregulated genes were interferon (IFN) regulatory factor family members, toll-like receptor (TLR) family members, IFN-β1, interleukin (IL)-1, C-C motif ligands, chemokine (C-X-C motif) ligands (CXCLs), and tumor necrosis factor (TNF). The strongest differential expression was observed in TNF, nucleotide-binding oligomerization domain-like receptor (NLR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways. At the late stage of infection, the most upregulated genes were CXCLs and ILs. The differentially expressed genes were divided into nine clusters, according to the time series expression trend. Next, the prominent activation of TLRs, retinoic acid-inducible gene I-like receptor signaling, NLRs, and downstream IFNAR-JAK-STAT signaling pathways were observed via a modified HSV-1 infection map. The HSV-1-induced upregulation of inflammatory cytokines in HGFs may drive inflammatory processes in periodontitis. The dynamic variations in mRNAs in HGFs from the early to late stages after HSV-1 infection can provide an analytical framework for determining the host anti-viral defense response to antagonize HSV-1 infection in periodontal tissues.

Lassa virus, the cause of deadly Lassa fever, is endemic in West Africa, where thousands of cases occur on an annual basis. Nigeria continues to report increasingly severe outbreaks of Lassa Fever each year and there are currently no approved vaccines or therapeutics for the prevention or treatment of Lassa Fever. Given the high burden of disease coupled with the potential for further escalation due to climate change the WHO has listed Lassa virus as a priority pathogen with the potential to cause widespread outbreaks. Several candidate vaccines have received support and have entered clinical trials with promising early results. This review focuses on the current state of vaccine and therapeutic development for LASV disease and the potential of these interventions to advance through clinical trials. The growing burden of LASV disease in Africa highlights the importance of advancing preclinical and clinical testing of vaccines and therapeutics to respond to the growing threat of LASV disease.

The use of bacteriophages for therapy has increased over the last decade. While there is need for clear regulatory pathways for bacteriophage approval for mainstream use in clinical practice, practitioners and patients have been able to access bacteriophage therapy under compassionate grounds and through magistral preparations. However, there is currently no standard for purifying these bacteriophages to ensure safety, and good manufacturing practice certification may not be achieved in these emergency uses. In this study, we employed an Interleukin Receptor Associated Kinase (IRAK) 3 knockout monocyte-based assay to evaluate the endotoxin removal efficacy of three common bacteriophage purification methods: Triton X-100 exposure, CsCl density gradient ultracentrifugation, and Pierce™ High-Capacity Endotoxin Removal Resin spin columns. In our experiments we tested these purification methods on three different bacteriophage morphotypes: siphovirus, podovirus and myovirus. We showed that the lowest endotoxin levels and immune responses were achieved when purifying bacteriophages with Triton-X treatment. The results from purifying with CsCl density gradient ultracentrifugation were comparable, and these were both significantly better than purification with Pierce™ High-Capacity Endotoxin Removal Resin spin columns. We also showed that Triton X-100 purification resulted in the lowest loss of bacteriophage titres. Finally, of the bacteriophages tested here, it did not appear that virus morphology affected efficacy of endotoxin removal.

The Flaviviridae family includes the dengue virus (DENV). About half of the world's population is in danger because of the estimated 390 million infections and 96 million symptomatic cases that occur each year. An effective treatment for dengue fever (DF) does not yet exist. Therefore, a better knowledge of how viral proteins and virus-targeted medicines may exert distinct functions depending on the exact cellular region addressed may aid in creating much-needed antiviral medications. Lipids facilitate the coordination of many viral replication phases, from entrance to dissemination. In addition, flaviviruses masterfully plan a significant rearrangement of the host cell's lipid metabolism to foster the growth of new viruses. Recent research has consistently shown the significance of certain lipid classes in flavivirus infections. For instance, in DENV-infected cells, overall cellular cholesterol (CHO) levels are only a little altered, and DENV replication is significantly reduced when CHO metabolism is inhibited. Moreover, statins significantly decrease DENV serotype 2 (DENV-2) titers, indicating that CHO is a prerequisite for the dengue viral cycle. Furthermore, many Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are now being evaluated in human research. A new pharmacological target for the management of high CHO is PCSK9. Moreover, suppression of PCSK9 has been proposed as a possible defense against DENV. Numerous studies have generally recommended the use of lipid-lowering medications to suppress the DENV. As a result, we have investigated the DENV and popular treatment techniques in this research. We have also examined how lipid metabolism, cellular lipids, and lipid receptors affect DENV replication regulation. Lastly, we have looked at how different lipid-lowering medications affect the DENV. This article also discusses the treatment method's future based on its benefits and drawbacks.