Virology Journal最新文献

In September 2023, five semi-domesticated reindeer calves (Rangifer tarandus tarandus) from Norrbotten County, Sweden, displayed clinical signs resembling contagious ecthyma. Samples were collected from the lesion sites, including the skin of the muzzle, eyelids, and oral mucosa. The samples were analysed via real-time PCR (qPCR) for parapoxviruses (PPV) and cervidpoxviruses (CvPV). Both viruses were detected in samples from several calves. Full genome sequencing of the PPV strain 23-MIK191411 revealed close similarity to the parapoxvirus red deer (RDPV) strain HL953 from a red deer (Cervus elaphus) in Germany but with a novel 2,187 bp insert in the right terminal third of the genome. This insert carried two open reading frames (ORFs) that, while divergent, presented sequence homology with several other PPVs. Analysis of amino acid differences relative to the sequence of the RDPV HL953 strain revealed that proteins implicated in host interactions and virulence presented the greatest differences. Thus, comparative sequence analysis indicates that an RDPV has recombined with an ancestor of 23-MIK191411 and adapted to the reindeer host. This study represents the first detection of RDPV, with a unique insert likely originating from an unknown PPV in reindeer, indicating its emergence beyond the red deer host range. Clinical signs are consistent with those caused by other poxviruses, including CvPV also detected in the investigated animal group, making it difficult to diagnose the causative agent solely via clinical observation. In the sequenced sample, RDPV was confirmed as the predominant variant. These findings underscore the importance of molecular diagnostics for accurate pathogen identification and highlight the need for continued health surveillance of reindeer. Further investigations are needed to determine the clinical impact of RDPV in reindeer.

Background: Long COVID presents significant health challenges, especially for patients with type 2 diabetes. Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT2) inhibitors may provide protective effects against COVID-19 complications, but their role in reducing long COVID risk remains unclear.

Methods: Utilizing the TriNetX platform, a retrospective cohort study was conducted among adults with type 2 diabetes diagnosed with COVID-19 between January 1, 2020, and June 30, 2024. Propensity score matching balanced demographic, clinical, and comorbidity profiles between SGLT2 inhibitor users and non-users. Cox proportional hazards regression assessed the risk of long COVID, defined by a spectrum of post-COVID-19 conditions.

Results: Among 5,162 matched pairs, SGLT2 inhibitor use was associated with a significantly lower risk of long COVID (HR = 0.85, 95% CI: 0.79-0.91). In the category of long-COVID symptoms such as abdominal symptoms, anxiety/depression, pain, headache, and cognitive symptoms, there were lower risks observed in the SGLT2 inhibitor group. Subgroup analyses showed consistent risk reduction across different age groups and sexes.

Conclusions: SGLT2 inhibitor use in patients with type 2 diabetes was linked to a reduced risk of long COVID. These findings suggest potential therapeutic benefits beyond glycemic control and highlight the need for further investigation into SGLT2 inhibitors as part of post-COVID-19 management strategies.

Lumpy Skin Disease (LSD), caused by the Lumpy Skin Disease Virus (LSDV), is a legally reportable disease recognized by the World Organization for Animal Health (WOAH) and has resulted in significant economic losses for the global cattle industry. Although several commercial LSDV vaccines are currently available, safer and more effective gene-deleted versions remain lacking. Therefore, screening key functional genes and developing gene-deleted live-attenuated vaccine strains hold substantial research value. In this study, we focused on ORF131, a gene whose function remains unclear. We successfully constructed an rLSDV-ΔORF131-EGFP gene deletion strain utilizing a homologous recombination, followed by purification using limiting dilution and single-cell subcloning techniques. Polymerase Chain Reaction (PCR) and Sanger sequencing validation confirmed that the deletion strain was successfully purified and free from wild-type virus contamination. Biological characterization indicated that the strain was genetically stable, with the optimal viral harvesting time in Madin-Darby Bovine Kidney (MDBK) cells being 72 h. Furthermore, RNA sequencing analysis of virus-infected cells revealed that rLSDV-ΔORF131-EGFP enhanced the immune and inflammatory responses of host cells compared to wild-type LSDV. This study not only provides a potential candidate strain for the development of an LSDV attenuated vaccine but also offers a theoretical foundation for the prevention and control strategies of LSD.

Background: Akabane virus (AKAV) is the causative agent of an economically significant disease in ruminants, manifested notably by outbreaks of abortion and congenital abnormalities. Vaccination stands as the primary defense against this disease. However, the development of safer, more stable, and efficient AKAV vaccines, including epitope-based designs, remains unexplored. Prior work by our group has pinpointed a neutralizing epitope, ¹¹³⁴SVQSFDGKL¹¹⁴², located in the Gc protein of AKAV. We further demonstrated its high degree of conservation across diverse AKAV genotypes.

Methods:  We produced and verified a novel virus-like particle (VLP) by incorporating the neutralizing epitope ¹¹³⁴SVQSFDGKL¹¹⁴² into a recombinant hepatitis B virus core antigen (HBcAg) scaffold. Then the immunogenicity of this VLP was evaluated by detecting the antibody titer targeting the AKAV Gc antigen and the neutralizing activity against AKAV in sera from the VLP-immunized mice. Furthermore, a preliminary indirect ELISA method was established based on this VLP for AKAV detection.

Results: The successful construction of VLP expressing the AKAV epitope was confirmed by using SDS-PAGE, followed by Western blot (WB) and transmission electron microscopy (TEM). Indirect ELISA results indicated that antisera from immunized mice contained antibodies specific to the AKAV Gc protein. Furthermore, neutralization assays demonstrated that the antisera could effectively neutralize AKAV in vitro and inhibit its replication in BHK-21 cells. The developed VLP-based indirect ELISA method successfully identified AKAV antibody-positive serum, with a detection sensitivity of up to a 1:1600 serum dilution.

Conclusions: In conclusion, we successfully constructed a VLP presenting the highly conserved neutralizing epitope of AKAV. This VLP is proved to be immunogenic and can serve as an effective coating antigen to establish an indirect ELISA method for AKAV detection. Collectively, our findings provide proof-of-concept for this epitope-presenting VLP as a promising candidate in the pursuit of a safe and effective epitope-based vaccine against AKAV and also highlight its utility as a diagnostic antigen for serological detection.

Akabane virus infection can cause abortion, stillbirth in pregnant ruminants, and congenital malformations in newborns. It is prevalent in most regions of Asia, as well as parts of Africa and Europe, causing severe impacts on the livestock industry. Inactivated vaccines are one of the effective means of disease prevention. In this study, an AKAV strain (CH-JL-01-2022) belonging to genetic group I was isolated, and based on this strain, an inactivated vaccine was developed, with screening conducted for the inactivating agent and adjuvant. Formaldehyde can completely inactivate AKAV, and mixed with the Imject^® Alum adjuvant can induce the high differentiation of CD4⁺ and CD8⁺ T-cells and produce high levels of TNF-α. High titers of neutralizing antibodies can be detected 21 days post-vaccination with inactivated virus and adjuvant mixture The viral load and lesions in some organs after virus challenge can be reduced. It was found that formaldehyde is the optimal Inactivating agent and Imject^® Alum is the best adjuvant, laying a foundation for the development of AKAV vaccines.

The recent global outbreak of Monkeypox virus since 2022, particularly outside Africa, has underscored its significant threat to public health. Genomic surveillance from multiple countries has revealed diverse genetic variations among circulating Monkeypox virus strains. Notably, a common F13L (E353K) mutation was identified in strains responsible for concentrated outbreaks in the United Kingdom and North America. The F13L is the current target of the only approved drug for poxvirus treatment, tecovirimat (previously known as ST-246), Previous studies have reported that the F13L (G277C) mutation significantly increases resistance. However, the impact of the shared F13L (E353K) mutation on viral transmission and its potential role in conferring tecovirimat resistance remains unclear. To address this, we employed homology modeling, molecular docking, and molecular dynamics simulations to investigate the phospholipase activity of the F13L protein. Our findings suggest that resistance to tecovirimat in F13L and its mutants may be attributed to altered flexibility of the drug-binding pocket and changes in the distance between the H334 residue and the fluorine atom in tecovirimat. This study provides a framework for rapidly assessing the resistance of emerging Monkeypox virus variants to tecovirimat and for guiding the rational modification of existing therapeutics to counter new viral threats.

Background: PROQUAD^®, a quadrivalent live-attenuated vaccine targeting measles, mumps, rubella, and varicella, is widely used in pediatric immunization programs. While clinical trials and post-marketing studies have established its general safety, real-world evidence from large-scale passive surveillance systems remains limited.

Methods: We performed a disproportionality analysis of PROQUAD-related adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS) between 2015 and 2025. Multiple statistical algorithms were applied to detect safety signals, supplemented by stratified analyses across age, sex, severity, and fatal outcomes.

Results: Among 17,234 reports, the most frequently reported AEs included injection site erythema, swelling, and fever, consistent with established reactogenicity. Several statistically significant signals not listed in the current FDA label were identified, such as febrile convulsion, vaccination failure, cyanosis, and influenza-like illness. These unlabeled events exhibited distinct patterns across age and sex subgroups, with serious and fatal outcomes occurring more frequently in children under three years of age and in medically vulnerable individuals. Most AEs occurred within three days of vaccination, although serious events showed delayed onset profiles.

Conclusion: This real-world pharmacovigilance analysis confirms the expected safety profile of PROQUAD while revealing additional adverse event signals that merit further clinical investigation and potential regulatory attention. Continued monitoring is essential to inform vaccine safety practices, particularly in pediatric populations with heightened susceptibility.

Background: Acinetobacter junii is an emerging opportunistic human and animal pathogen, fast gaining antimicrobial resistance. As conventional treatment becomes ineffective, alternatives are needed to address this challenge. Bacteriophages offer a promising yet underexplored solution in combating A. junii infections. Here, we report the isolation and characterisation of a temperate phage, ɸPh_AJ01, effective against a carbapenem-resistant A. junii. Moreover, the study adopts a technique for biasing the temperate phage to the lytic life cycle to address the issues of lysogeny. The efficacy of the phage in rescuing A. junii-infected Caenorhabditis elegans is also demonstrated.

Methods: Phage ɸPh_AJ01 was isolated and purified from the Cooum River in Chennai, India. Host range analysis, adsorption assay, growth curve, and in vitro bacteriolytic test were performed. Transmission electron microscopy and whole-genome sequencing were carried out to understand its morphological and genetic features. Phage stability was tested in different temperatures and pH conditions. Antibiofilm activity of the phage was studied using inhibition and disruption assays. Bacteriophage-insensitive mutation frequency of A. junii was evaluated by the patch screen test. Experiment to bias the temperate phage towards lytic life cycle and, survival assay with A. junii-infected C. elegans were also performed.

Results: ɸPh_AJ01 is a temperate, narrow-spectrum, icosahedral, tailed phage that efficiently infected A. junii, yielding a burst size of 74 ± 8 virions per cell with good temperature and pH stability. ɸPh_AJ01 inhibited biofilm formation by 92%, and disruption by 73.8%. A. junii gained resistance to ɸPh_AJ01 at a frequency of 6.88E-06 CFU/mL. The double-stranded DNA genome of 44,561 bp and GC content of 38.62%, encodes 65 open reading frames. The phage is novel, with only 80% similarity to other Acinetobacter phages. The genome is devoid of antibiotic-resistant and virulence genes. The temperate phage, when biased with ciprofloxacin (50 ng/mL), resulted in ≥ 5 log reduction of A. junii, with an associated 6-log reduction in lysogens and 5-fold increase in phage titre. The in vivo study yielded a 65% increase in survival of A. junii-infected C. elegans with the phage and ciprofloxacin when compared to 28% with phage alone.

Conclusions: The study describes the isolation and characterisation of a temperate phage ɸPh_AJ01 against A. junii. A lysogeny biasing strategy was additionally evaluated under both in vitro and in vivo conditions to address the limitations of the temperate phage.

Mango (Mangifera indica), a globally significant fruit crop, is susceptible to diverse pathogens that threaten its productivity. High-throughput sequencing-based virome profiling and Sanger sequencing of symptomatic (mosaic, upward leaf curling with undulated margin in the young leaves) mango samples revealed the presence of a novel olivavirus (mangifera virus 1, MaV-1), and a benyvirus (mangifera indica latent virus, MiLV). Comparative genomic and phylogenetic analyses confirmed the taxonomic placement of MaV-1 within the proposed genus Olivavirus, based on conserved domains and sequence divergence in the RdRp, HSP70h, and coat protein genes. This study represents the first report of MiLV in India and a novel MaV-1 species infecting mango worldwide. Current study enhances understanding of mango viral spectrum and highlights the need for viral surveillance to address the potential threats to mango cultivation.