Virology Journal最新文献

Background: Cell-free DNA (cfDNA) has emerged as a relevant biomarker reflecting disease severity in hospitalised COVID-19 patients, correlating with respiratory failure and mortality. However, its utility has not yet been evaluated in general practitioner setting.

Methods: A prospective single-centre, two-arm, parallel, longitudinal cohort study conducted in a German general practice with four doctors between 8/2021 and 4/2022.

Participants: Sixty-one outpatients with flu-like symptoms participated: 31 (10 men, 21 women) tested SARS-CoV-2 positive (COVID group); 30 (12 men, 18 women) were controls (control group). The groups were demographically similar.

Primary outcome measures: Comparison of cfDNA levels between groups at day 0, 7 and 14.

Secondary outcome measures: Correlations between cfDNA levels and laboratory and clinical parameters like blood counts, respiratory rate and oxygen saturation.

Results: cfDNA levels did not differ significantly between groups (F [1, 59] = 1.538, p = 0.22): day 0: mean (± standard deviation) = 14.45 (± 6.24) ng/ml (COVID group) vs. 11.32 (± 4.79) ng/ml (control group); day 7: 14.46 (± 6.57) ng/ml vs. 12.53 (± 6.67) ng/ml; day 14: 12.94 (± 6.66) ng/ml vs. 12.93 (± 7.02) ng/ml. However, at t0, the integrity index was significantly lower in the COVID group (t0: 0.30 [±- 0.15] vs. 0.41 [± 0.1]; p = 0.0127) increasing at t1 (0.38 [± 0.17]; p = 0.008) and at t2 (0.42 [± 0.22]; p < 0.001).

Conclusion: Unlike hospitalised patients, cfDNA levels did not differ significantly between outpatient groups. Therefore, a decision on the need for hospitalisation based on clinical and serological factors is still required. The significantly lower integrity index of the SARS-CoV-2 infected individuals indicates that their DNA kinetics differ from those of individuals infected with other respiratory pathogens.

Trial registration: German Clinical Trials Register: DRKS00024722, Registration date: 10 March 2021.

Background: Bovine coronavirus (BCoV) causes neonatal calf diarrhea (CD), winter dysentery in young cattle (WD), and respiratory system infections in cattle of all ages worldwide. The aim of this study was the detection, isolation, and investigation of the frequency, and molecular characterization of circulating BCoVs in cattle in the Thrace district of Türkiye. It was also aimed to determine genotypes and variants to include in vaccine and vaccination strategies.

Methods: For this purpose, a total of 47, including 12 integrated and 35 small-scale farms located in the Thrace district bordering European Union, were visited. A total of, 281 samples, consisting of 189 nasal/oropharyngeal and 92 fecal swabs were collected from calves exhibiting diarrhea and respiratory signs. RNA was extracted from samples and SYBR-Green real-time RT-PCR was performed. Phylogenetic and heatmap analyses were made using the sequences obtained from RT-PCR. Virus isolation was performed in HRT-18 cells using trypsin.

Results: BCoV RNA was detected in 22.06% (62/281) of swabs collected from calves under 6 months with enteric and/or respiratory signs. Detection rates were 21.69% (41/189) in nasal/oropharyngeal and 22.82% (21/92) in fecal swabs. The virus was identified in 95.7% (45/47) of sampled farms. Statistical analysis showed no significant association between BCoV positivity and the vaccination status of animals. Phylogenetic studies of S1 gene region have indicated that the samples detected in the Thrace district were clustered within the GIb subgroup along with European strains (97.6-100%, nucleotide similarity). These samples also exhibited high nucleotide similarity with HECV-4408 from human CoVs (98.28-99.14%) and DcCoV-HKU23 from other animal CoVs (97.85-99.14%). Despite being collected from distinct regions and years, two field isolates exhibited complete nucleotide identity. BCoV was successfully isolated from both nasal/oropharyngeal and fecal swabs.

Conclusions: This study indicates that BCoV remains a health concern in calves in Türkiye, with isolates clustering in the GIb subgroup alongside European strains. Strengthening biosecurity and regular monitoring should remain priorities; collecting immunologic and field-effectiveness data will help guide the development of regionally updated vaccination strategies. A One Health approach that combines full-genome sequencing with epidemiological studies would help assess zoonotic potential.

Background: At present, the Monkeypox virus (MPXV) outbreak has become a significant public health concern, and its severity is increasing based on different clades globally, which, combined, are leading to severe complications. However, it was observed that MPXV infection was highly expressed in individuals with Human Immunodeficiency Virus (HIV), and the mechanism of cross-talk has not been explored.

Methods: This study employed a network-based methodology to examine the role of differentially expressed genes (DEGs) in HIV and monkeypox (Mpox) infections. The commonly shared DEGs in Mpox and HIV were examined, followed by their functional enrichment, co-expression, transcriptional factor, potential correlation with disease, and promising drug-associated network. Additionally, the docking analysis was accomplished to gain the interaction site of the compound towards these target genes.

Results: The GEO datasets of Mpox and HIV were examined, wherein a total of 570 Mpox and 642 HIV DEGs were identified. Among them, 41 DEGs were common, and functional enrichment and pathway analysis revealed their involvement in vital biological functions and pathways. Further, the PPI and co-expression analysis of these genes was conducted, which revealed 8 key genes or hub genes, which included SOCS3, NFKBIA, IFIT1, CCNB2, PLK3, PTGS1, ZFP36L2, and RGS16. Moreover, transcription factors (TFs) and miRNAs of the hub genes were also examined, which offered new insight into potential therapeutic targets. The gene-disease network also revealed several other diseases linked to the common and hub genes. Subsequently, the docking analysis revealed that the selected compound actively bound to the target genes and could be a potential lead to combat this.

Conclusions: This study unveils the shared mechanism between HIV and Mpox based on the hub genes perspective, offering new insights into co-infection and highlighting potential possibilities for simultaneous therapeutic intervention in both diseases.

Nucleotide (nt) deletions in the VP1 region of poliovirus are extremely rare. However, as early as 2012, we detected a natural type 2 poliovirus strain in sewage, originating from the Sabin 2, which exhibited such deletions. Whole-genome analysis revealed that the virus genome is 7,436 nt in length, with three nucleotide deletions in positions 16-18 of the VP1 region (2,497-2,499 nt), resulting in a deletion of the amino acid at position six of the VP1 capsid protein. Notaly, the missing amino acids are not located at known attenuation or neutralization sites. In addition, the important attenuated sites at positions 481 and 2,909 remained unchanged. Only one substitution was observed at the known neutralizing antigen site: VP3-61 (Arg to Lys) on NAg3a. Recombinant analysis showed that the virus is a type 2/3 recombinant virus, with the crossover site located between nucleotides 6,981 and 7,439, spanning the 3D^pol region and the 3' untranslated region (UTR). The protein structure simulation showed that VP1 capsid protein of the PV-2 deletion variant was very similar to Sabin 2. In the VP1 region, the PV-2 deletion variant has only a triple nucleotide deletion, with no other mutations, indicates that the virus was in an early stage of evolution before being isolated from sewage. Furthermore, this variant is only a type 2/3 recombinant, not recombined with other non-polio enteroviruses, suggesting a short transmission and circulation time of the virus in the population. Therefore, we speculate that the nucleotide deletion in VP1 region of poliovirus may occur in the early evolutionary stage. Although the virus has not yet spread widely among humans, these findings highlight the importance of continuous environmental monitoring of poliovirus.

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.