Virology Journal最新文献

Background: Nudix enzymes constitute a family of hydrolases that share a conserved Nudix motif, which catalyzes the hydrolysis of nucleoside diphosphates linked to another moiety X. Some members are cellular and viral decapping enzymes that hydrolyze the 5´ cap structure on an mRNA molecule. Unlike vaccinia virus, which encodes two Nudix enzymes, orf virus (ORFV) encodes only a single Nudix-containing gene, ORFV071 (OV71). This study investigates the biochemical properties of recombinant OV71 protein and its role in viral replication.

Methods: In vitro decapping assays using radiolabeled capped RNA substrates were performed to assess OV71 activity in the presence or absence of competitors or metal cations. Electrophoretic mobility shift assays and pulldown assays evaluated the RNA-binding ability of OV71. Decapping-deficient mutant viruses were generated by homologous recombination, and their replication was analyzed using one-step growth curve experiments. Reverse transcription-qPCR quantified host and viral mRNA levels.

Results: OV71 exhibited intrinsic decapping activity, hydrolyzing long capped RNAs to release m⁷GDP, with optimal activity in the presence of Mn²⁺. It bound both single- and double-stranded RNA and was expressed early during viral replication. Decapping-deficient mutant viruses replicated poorly in cells. Unlike the vaccinia virus decapping-deficient mutant, which triggers host antiviral responses leading to degradation of viral and host mRNAs as well as rRNAs, an orf virus mutant caused accumulation of host-capped RNAs and a severe reduction in viral mRNAs. Notably, host rRNA remained relatively intact compared to wild-type virus infection.

Conclusion: OV71 is a decapping enzyme that hydrolyzes the cap structure on long capped mRNAs. It binds both single- and double-stranded RNA, suggesting that it may target both RNA species in infected cells. Its decapping activity is critical for efficient orf virus replication. Loss of this activity leads to the accumulation of host-capped mRNAs, a drastic reduction of viral mRNAs, and minimal impact on host rRNAs, indicating a role distinct from that of the vaccinia virus decapping enzymes.

Background: Rabies, a lethal viral encephalitis caused by Rabies virus (RabV), is transmitted via bites, scratches, or mucosal contact with infected animals, as well as through inhalation of aerosolized particles, ingestion of contaminated raw animal products, or transplantation of infected organs. It's near-universal fatality, diverse transmission routes, and marked clinical variability significantly impede timely diagnosis, highlighting the demand for a rapid and precise diagnostic approach.

Methods: Single-center retrospective case series.

Results: This series reported three rabies cases admitted to the First People's Hospital of Qinzhou: one without identifiable exposure and two with confirmed exposure histories. Clinical presentations were highly variable and diagnostically misleading. Application of Probe-Capture Metagenomics (pc-mNGS) to cerebrospinal fluid and blood samples enabled direct identification of RabV and concurrent detection of coexisting pathogens.

Conclusion: pc-mNGS demonstrates potential as a rapid, economical diagnostic tool capable of detecting RabV in specimens with low viral loads-such as blood and cerebrospinal fluid-from both exposed and unexposed individuals. Simultaneous identification of additional pathogens further supports its diagnostic utility.

Since its emergence in late 2019, SARS-CoV-2 has evolved into multiple variants with distinct genetic and clinical features. Among them, the Omicron variant (B.1.1.529) and its sublineages BA.2.75, JN.1.8, and KP.2 have shown enhanced transmissibility and immune evasion, while generally exhibiting reduced lower respiratory tract pathogenicity compared to earlier variants, thereby continuing to pose significant challenges to public health. In India, these variants have significantly shaped the trajectory of the pandemic, necessitating focused evaluation of their biological and clinical impact. This review aims to provide a comprehensive study on the virology, pathophysiology, and systemic manifestations of Omicron and its emerging subvariants upto July 2025. We discuss their mechanisms of entry and replication, interaction with ACE2 and TMPRSS2 receptors, and evasion of host immune responses. Particular emphasis is placed on multi-organ involvement beyond the respiratory system, including neuro-respiratory dysregulation, cardiovascular complications, hepatic injury, gastrointestinal disturbances, and renal dysfunction. Furthermore, we evaluate the effectiveness of available vaccines, antiviral therapies, and diagnostic tools, alongside emerging clinical strategies such as vagus nerve stimulation, thermal modulation, and respiratory muscle training. By integrating molecular insights with clinical outcomes, this review highlights the multifaceted and systemic nature of Omicron-induced disease. We underscore the urgent need for variant-specific immunisation, early intervention strategies, and robust genomic surveillance to mitigate long-term sequelae and guide preparedness for future outbreaks.

Background: Viral meningitis is a frequent cause of central nervous system (CNS) inflammation, typically presenting with headache, fever, photophobia, and neck stiffness. While enteroviruses and herpes simplex virus are the most common etiologies, Human Herpesvirus 7 (HHV-7), a rarely recognized cause, is increasingly implicated in aseptic meningitis, particularly in immunocompetent adults. HHV-7 is a T-lymphotropic virus that primarily affects CD4 + T lymphocytes, and it is globally prevalent, with over 95% of adults seropositive for the virus. Though traditionally associated with mild childhood diseases like exanthems and febrile seizures, HHV-7 has been linked to neurological complications, including meningitis, encephalitis, and myelitis. A 37-year-old Italian female with a 10-year history of vegetarianism and a 2-year history of pap smear-diagnosed Human Papillomavirus (HPV)-associated low-grade squamous intraepithelial dysplasia was admitted for a 3-day history of progressive worsening lower back pain radiating to bilateral posterior lower limbs and soles paresthesia. Physical examination shows bilateral positive Lasegue sign, bilateral pain upon palpation of 4/4 Valleix's points, and absence of ankle reflexes, otherwise intact. Initial blood laboratory investigations reveal mild leukocytosis (10.92 G/L) with normal C-reactive protein (CRP), folate, and cobalamin. Cerebrospinal fluid (CSF) analysis shows 441 white blood cells/mm³, elevated protein (1.073 g/L), and positive Pandy reaction. HHV-7 was detected via CSF polymerase chain reaction (PCR); other bacterial and viral pathogens were negative. Patient demonstrates remarkable recovery after 5 days, along with pain control.

Conclusion: We report a rare case of viral meningitis induced by HHV-7 in a 37-year-old immunocompetent female, whose initial symptoms were unusual, presenting primarily with lower limb pain and numbness. Laboratory tests revealed HHV-7 deoxyribonucleic acid (DNA) in the CSF, confirming the diagnosis of aseptic meningitis. This case emphasizes the importance of considering HHV-7 in the differential diagnosis of viral meningitis, even without classic systemic signs. Despite the absence of specific antiviral therapy for HHV-7, supportive care remains effective. This case adds to the growing evidence on HHV-7 as an under-recognized cause of aseptic meningitis, particularly in immunocompetent individuals.

Background: Amidst rising antimicrobial resistance, bacteriophage (phage) therapy has re-emerged as a pivotal weapon against multidrug-resistant pathogens. Jumbo phages, distinguished by large genomes, show particular therapeutic promise. Yet current understanding of jumbo phages is still lacking.

Methods: Phage was isolated from domestic sewage. The biological properties of JP4 was characterized via transmission electron microscopy, stability tests, one-step growth curve. The genome of JP4 were elucidated by sequencing and bioinformatics tools. Structural proteins were identified via mass spectrometry. Bactericidal and biofilm eradication activities were evaluated using bacterial turbidity measurements and crystal violet assays, respectively. Statistical significance was determined by using one-way ANOVA in GraphPad Prism.

Results: Phage JP4 has an icosahedral head (approximately 110 nm in diameter) and a contractile tail (about 120 nm in length). JP4 possesses a linear dsDNA genome of 370,741 bp, encoding 738 proteins and 8 tRNAs. Phylogenetic analysis revealed that JP4 is a new member of the Asteriusvirus genus, and shares close evolutionary relationships with Escherichia phage UB. Additionally, mass spectrometry identified four novel structural protein encoding genes of JP4. Phage JP4 exhibited rapid infection cycle, high stability, potent in vitro bactericidal activity, and strong inhibitory effect on E. coli biofilms.

Conclusions: Phage JP4 is a new member of the Asteriusvirus genus. As a lytic jumbo phage with rapid bactericidal activity and strong biofilm degradation capacity, JP4 is a promising therapeutic candidate against E. coli O157:H7 infections. This study provides insights into the diversity and clinical potential of jumbo phages in combating pathogens.

The Rabbit Hemorrhagic Disease Virus (RHDV) represents a significant threat to rabbit populations globally, affecting both wild and domesticated rabbits, with mortality rates ranging from 50% to 90%. Despite its severity, there is currently no specific treatment available for RHDV. This study investigates the potential of natural compounds derived from Nigella sativa as antiviral agents against RHDV. Molecular docking analysis was conducted to explore the interaction between eleven compounds from Nigella sativa and the two key proteins of RHDV, viral protein genome-linked (VPg) and RNA-dependent RNA polymerase (RdRP), as key proteins involved in viral replication. Explicit-solvent MD (100 ns, 310 K) was performed for four top complexes (VPg/RdRP with nigellidine and dithymoquinone), tracking backbone/ligand RMSD, radius of gyration, H-bond counts, and per-residue RMSF, with equilibrated frames analyzed by PCA and MM-GBSA. The results revealed successful docking of all compounds from Nigella sativa to both VPg and RdRP proteins. From Nigella sativa compounds, Nigellidine and Dithymoquinone displayed strong interactions with VPg and RdRP and formed various hydrogen bonds and hydrophobic interactions, indicating their potential as inhibitors of viral replication. Interestingly, all ligands demonstrated favorable drug-likeness properties, adhering to Lipinski's Rule of Five and exhibiting desirable pharmacokinetic profiles. Thymohydroquinone and nigellidine displayed the highest lipophilicity, suggesting their potential for efficient tissue penetration and distribution. Complexes remained stable and retained poses, with reduced pocket flexibility, favorable MM-GBSA ΔG_bind, and tighter PCA clustering-supporting sustained binding and pocket stabilization. These findings suggest that compounds from Nigella sativa show promise as natural antiviral agents against RHDV. Nevertheless, additional experimental validation through in vitro and in vivo studies is essential to confirm the effectiveness and safety of these compounds for treating RHDV infection.

Giant virus discovery in 2003 revolutionized the virus paradigm. In 2015, we introduced a new host, Vermamoeba vermiformis, that led to the discovery of Faustovirus, Orpheovirus and two giant viruses (Clandestinovirus and a faustovirus) having distinct cytopathic effects despite being co-isolated from the same environmental sample and culture. This raised concerns about the possibility that the most "discreet" virus be overlooked. Here we report on Usurpativirus, a new giant virus closely related to Clandestinovirus and co-isolated with Faustovirus LCD7 in V. vermiformis. Its non-lytic replicative cycle was primarily overlooked in presence of the lytic Faustovirus. The Usurpativirus genome encode two tRNAs and 758 predicted proteins, and share 707 and 202 orthologs with Ushikuvirus and Clandestinovirus, respectively. We detected four histone-like proteins that further challenge the compaction of DNA from these large genomes into icosahedral capsids of approximately 240 nm, as well as four capsid-associated proteins, but we did not detect any predicted proteins involved in entry/fusion that could explain the special replication strategy of this virus. Scanning electron microscopy revealed two distinct morphologies for amoebae infected with Usurpativirus, which became either rounded with a smooth surface or more flattened with a wavy surface. In addition, virions were observed attached to the outside of the amoebae, which most often had a smooth surface and rarely an undulating surface after 6 days of infection. Finally, such co-infection with two distantly-related giant viruses questions on the possible interactions between each other.

Okutama tick virus (OKTV) is a novel tick-borne RNA virus that has been reported in Japan and China. In the present study, an OKTV was detected in Haemaphysalis flava that had bitten a raccoon dog in South Korea by reverse transcription polymerase chain reaction using viral family-specific primers. Whole-genome sequencing revealed that the South Korean OKTV strain contains L and S segments with lengths of 6,529 and 1,890 nucleotides, respectively. Phylogenetic analyses revealed that OKTV strains formed two clusters based on the L segment and three clusters based on the S segment, with the South Korean strain forming a common cluster with three Chinese strains (SDQDH01, SDQDH04, and SDQDR04). Sequence comparisons showed high conservation among OKTV strains, with nucleotide identities of at least 97.74% and amino acid identities of at least 98.53% for both the L and N genes. Notably, the South Korean strain exhibited the highest amino acid similarity with the Chinese strain SDQDH04 (99.86% similarity in RdRP and 100% similarity in N protein). Selection pressure analyses revealed low dN/dS ratios for the L (0.0326) and N (0.0927) genes, with no sites detected under positive selection. Collectively, this study provides the first genomic characterization of OKTV in South Korea, expanding its geographical distribution and contributing to our genetic understanding of this virus. Although infectivity in animal hosts has not been established, further studies are needed to assess the zoonotic potential of OKTV.

Background and objectives: Dengue is one of the fastest spreading arboviral infection with no specific antiviral treatment, making vaccination a significant preventive approach. Several dengue vaccines have been developed, but their efficacy, safety, and serotype-specific protection remain areas of concern. Over the past five years, new clinical data have emerged, influencing vaccine recommendations and deployment strategies. This systematic review analyses recent dengue vaccine data, assessing their effectiveness, and safety profiles.

Methods: Data was taken from three different databases i.e. PubMed, Cochrane and google scholar from last five years (2020-2025) by using the specific search terms. Filters were applied to extract the studies relevant to our analysis. Data was analysed and forest plots were made for proper understanding of vaccine efficacy and safety data of vaccines.

Results: 14 studies are included in the study and our systematic review study on dengue vaccines revealed TAK-003 and TV005 with highest protection rates in their respective settings. Safety profiles varied: TAK-003 and CYD-TDV reduced serious events, whereas TV005 was associated with heightened reactogenicity.

Conclusion: This review provides a systematic review of the dengue vaccines data available from the last five years highlighting significant progress in vaccine development, efficacy, and safety and TAK-003 showed the greatest efficacy against hospitalized and symptomatic Dengue patients, reducing risk by 85% (RR 0.15; 95% CI 0.07-0.33).

Purpose: To identify early predictive factors for hepatitis B surface antigen (HBsAg) clearance at week 48 following pegylated interferon (Peg-IFN) therapy in inactive HBsAg carriers (IHC), and to develop an early machine learning-based model to assist clinical decision-making.

Methods: This retrospective analysis was based on a multicenter, prospective cohort and included 777 IHC patients who received at least 48 weeks of Peg-IFN therapy. Least Absolute Shrinkage and Selection Operator (LASSO) regression and the Boruta algorithm were applied to select predictive variables. Nine machine learning models-including logistic regression (LR), decision tree (DT), and random forest (RF)-were constructed and evaluated using 10-fold cross-validation. An external validation cohort (n = 167) from three medical centers in Beijing was used for model validation. SHapley Additive exPlanations (SHAP) values were used to interpret variable contributions.

Results: The overall HBsAg clearance rate at week 48 was 29.9% (232/777). Key predictors included baseline HBsAg level, HBsAg decline > 1 log IU/mL at week 12, and the ratio of alanine aminotransferase (ALT) to HBsAg at week 12. The RF model demonstrated the best performance with an area under the curve (AUC) of 0.829 (95% CI: 0.784-0.874) and specificity of 0.774 in the training set, and an AUC of 0.838 (95% CI: 0.759-0.917) with specificity of 0.968 in the external validation set. SHAP analysis showed that baseline HBsAg had the highest predictive importance.

Conclusions: The RF-based model accurately predicts HBsAg clearance in IHC patients undergoing Peg-IFN therapy and offers a promising tool for early identification of candidates for individualized treatment strategies.