Viruses-Basel最新文献

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Previous studies have reported the propagation of diverse HIV-1 CRFs of South American origin in Europe. Here, through protease-reverse transcriptase (Pr-RT) and integrase sequence analyses, we identify a Spanish cluster (BC3) branching with a Brazilian virus (10BR_RJ009) previously classified as CRF146_BC. In Pr-RT, BC3 comprised 14 viruses and was nested within a larger cluster, comprising 22 Brazilian viruses and 1 Spanish virus branching outside of BC3. Near full-length genome analyses of five BC3 viruses revealed mosaic structures identical to 10BR_RJ009, with two breakpoints delimiting a ~0.3 kb subtype B fragment within an otherwise subtype C genome. Two other Brazilian viruses previously classified as CRF146_BC (10BR_RJ039 and 01_BR_RGS69) had one and two additional short subtype B fragments, respectively, and failed to group with the 10BR_RJ009/BC3 cluster in subtype C fragments. Based on these results, we contend that 10BR_RJ009 and BC3 viruses, but not 10BR_RJ039 and 01_BR_RGS69, should be classified as CRF146_BC. Bayesian analyses estimated the CRF146_BC emergence in Brazil to be around 1999 and its introduction in Europe around 2011. CRF146_BC is the 10th CRF of South American origin reported to circulate in Europe, reflecting the relationship between South American and European HIV-1 epidemics.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus prevalent in more than 110 countries and regions, including Africa, Asia, the Americas, and Europe. It can cause acute fever, rash, and severe joint pain, and some patients may develop chronic arthritis, which significantly impairs quality of life. CHIKV infection can occasionally be fatal, with neurologic disease a particularly severe manifestation. Following its resurgence in 2005, CHIKV has emerged as a major threat to global public health. This review summarizes diagnostic techniques, advances in vaccine development, and the latest drug interventions for CHIKV. We also present an overview of the epidemiology, structure, and invasion mechanisms of epidemic hotspots in 2024-2025 and propose evidence-based strategies for effective prevention and control of CHIKV infection.

Phage therapy is the use of bacterial viruses, or bacteriophages, as antibacterial agents. It has been in use for over 100 years and is becoming increasingly common clinically. The first steps of phage therapy include identification of bacteria to be targeted and then obtaining phages with appropriate host ranges. This is followed by various approaches to in vitro phage characterization. Increasingly common for phage phenotypic characterization is the use of kinetic microtiter plate readers. They can both decrease workloads and increase throughput, especially relative to analyses that require plating on agar-based media. These colorimetric/turbidimetric/optical density approaches primarily assess phage-induced culture-wide bacterial lysis, in the shorter term, or instead the phage potential to suppress phage-resistance evolution over longer time frames. Considered here are methods relevant to phage characterization especially for phage-therapy purposes. Discussed are turbidity-reduction assays, determinations of phage antibacterial virulence, and related time-kill curve analysis. All are or can be optical density-based approaches to assessing phage-based bacterial reduction. Emphasis is placed on consideration of the utilities, limitations, and intersections of these similar methods. Emphasized is that the start of "Deviation"-where phage-treated culture turbidity diverges from phage-free controls-may represent a superior endpoint for such optical density-based bacterial-reduction protocols.

The poly(A) tail on viral mRNAs plays an important role in gene expression, given the role of the 3' mRNA tail in mRNA stability and translation. Viruses have developed several strategies to maintain the integrity of their poly(A) tails. These include attracting stabilizing proteins through elements in the 3' untranslated regions of their mRNA, remodeling their poly(A) tails using terminal nucleotidyl transferases, and blocking deadenylase access to the terminal 3' end of their poly(A) tails using protein-protein interactions or through triple helical RNA structures. Collectively, the presence of these multiple strategies illustrates the vital overall need for viruses to maintain and preserve their poly(A) tails, highlighting a potential avenue for broad-spectrum antiviral development. In addition, poly(A) tail preservation strategies used by viruses may also be applied to RNA vaccines and therapeutics.

Tilapia lake virus (TiLV) is a highly virulent pathogen that has caused substantial mortality in tilapia farms, particularly those with open-water systems. However, TiLV can also emerge and persist in closed environments, such as recirculating aquaculture systems (RAS), where environmental accumulation and repeated exposure may intensify infection and sustain outbreaks. In this case study, we conducted three field experiments to better understand TiLV dynamics among Nile tilapia in RAS. In experiment I, we quantified the TiLV levels in the fish, water, and sediment to compare outbreak and no-outbreak conditions and found that the TiLV concentrations in liver samples and the water were significantly higher in the outbreak ponds and positively correlated with increased fish mortality. In experiment II, we used a side-by-side field trial to evaluate the protective efficacy of a TiLV vaccine and its effects on the viral loads in the fish and aquatic environment during outbreaks. The vaccinated fish showed substantially lower cumulative mortality (16.7%) than the unvaccinated controls (37.7%), with a relative percent survival of 55.6%. Additionally, the TiLV concentrations in the pond water of the vaccinated group were significantly lower. In experiment III, we compared the TiLV patterns between RAS and non-RAS operations to determine how water recirculation influences viral accumulation and outbreak severity. The results revealed limited viral accumulation and shorter disease outbreak duration in the non-RAS. Overall, our findings showed that the TiLV levels in the rearing water were closely linked with disease severity in the RAS-based tilapia hatcheries. Continuous water recirculation allowed the virus to build up in the system, which led to more prolonged outbreaks, while the non-RAS conditions with regular water discharge showed lower viral loads and faster recovery. The vaccinated fish had better survival rates and released less virus into the water, which helped reduce infection pressure across the ponds. Together, these results suggest that combining vaccination with good water management and molecular monitoring can provide a practical, noninvasive way to detect and control TiLV outbreaks in intensive farming systems.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy caused by persistent infection with human T-cell leukemia virus type 1 (HTLV-1). ATLL remains difficult to treat despite intensive chemotherapy, antiviral therapy, and hematopoietic stem cell transplantation. The limited durability of current treatment strategies highlights the need for mechanism-based therapeutic approaches. Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that regulates transcription, RNA splicing, DNA damage responses, and immune signaling through symmetric dimethylation of histone and non-histone substrates. PRMT5 is frequently overexpressed across hematologic and solid tumors. Preclinical studies indicate that PRMT5 expression is elevated during HTLV-1-mediated T-cell transformation and that pharmacologic inhibition of PRMT5 selectively impairs the survival and transformation of infected T cells in vitro and in vivo. In this review, we highlight the current understanding of PRMT5 biology in cancer, summarize preclinical studies supporting PRMT5 as a therapeutic target in ATLL, and discuss key challenges to future clinical translation. We also discuss emerging approaches such as rational combination therapies and tumor-selective PRMT5 inhibitors as potential paths toward treatment for ATLL.

Respiratory viruses such as SARS-CoV-2, influenzas A and B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human parainfluenza virus type 3 (HPIV-3), and rhinoviruses remain major causes of global morbidity. Their rapid evolution, high transmissibility, and limited therapeutic options, together with the absence of approved vaccines for several pathogens, highlight the need for broad-acting and pathogen-independent antiviral strategies. Nitric oxide exhibits antiviral activity through redox-dependent mechanisms, including S-nitrosylation of cysteine-containing viral proteins and disruption of redox-sensitive structural domains. Clinical studies conducted during the SARS-CoV-2 pandemic demonstrated that a nitric oxide nasal spray (NONS) rapidly reduced nasal viral load and transmission. In this study, we evaluated the in vitro virucidal activity of the NONS against a panel of clinically relevant respiratory viruses representing four major virus families. Virus suspensions of approximately 10⁴ CCID₅₀ were exposed to a full-strength NONS for contact times ranging from 5 s to 2 min at room temperature, followed by neutralization and quantification of residual infectivity using endpoint dilution assays. The NONS rapidly reduced viral infectivity across all viruses tested, achieving >3 log₁₀ reductions within 2 min. SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, Omicron BA.1, and XBB 2.0 were reduced to levels at or below the assay detection limit within 30 s to 2 min. Influenza A and B viruses showed the fastest loss of infectivity, reaching detection limits within 10-15 s. RSV, hMPV, HPIV-3, and human rhinovirus 14 were similarly inactivated within 1-2 min. These findings demonstrate that the NONS exhibits rapid and broad-spectrum virucidal activity against diverse respiratory viruses and supports its potential role in pandemic preparedness but also seasonal use.

Influenza-associated encephalitis/encephalopathy (IAE) is a severe neurological complication characterized by central nervous system dysfunction and structural damage following influenza virus infection. Predominantly affecting infants and young children, IAE exhibits its highest incidence in those under five years of age. Key clinical manifestations of IAE include acute seizures, sudden high fever, and impaired consciousness, frequently progressing to coma. Neuroimaging, particularly magnetic resonance imaging (MRI), often reveals multifocal brain lesions involving multiple brain regions, including the cerebellum, brainstem, and corpus callosum. The prognosis of IAE is poor, with a mortality rate reaching 30%. Current diagnosis relies heavily on clinical presentation and characteristic neuroimaging findings, as the precise pathogenesis of IAE remains elusive. While various research models, including cell lines, brain organoids, and animal models, have been developed to recapitulate IAE features, significant limitations persist in modeling the core clinical pathophysiology observed in pediatric patients, necessitating further model refinement. This review synthesizes the clinical spectrum of IAE, summarizes progress in understanding its pathogenesis, and critically evaluates existing research models. We aim to provide a foundation for utilizing experimental approaches to elucidate IAE mechanisms and identify potential therapeutic strategies.

Influenza D virus (IDV), an emerging orthomyxovirus with zoonotic potential, infects diverse hosts, causes respiratory disease, and remains poorly characterized in China despite its global expansion. From October 2023 to January 2025, we collected 563 nasal swabs from cattle across 28 farms in Jilin Province, Northeast China, and identified seven IDV-positive samples (1.2%), recovering two viable isolates (JL/YB2024 and JL/CC2024). Full-genome sequencing revealed complete, stable seven-segment genomes with high nucleotide identity (up to 99.9%) to contemporary Chinese D/Yamagata/2019 strains and no evidence of reassortment. Maximum-likelihood and time-resolved Bayesian phylogenies of 231 global hemagglutinin-esterase-fusion (HEF) sequences placed the Jilin isolates within the East Asian D/Yamagata/2019 clade and traced their most recent common ancestor to approximately 2017 (95% highest posterior density: 2016-2018), suggesting a cross-border introduction likely associated with regional cattle movement. No IDV was detected in parallel surveillance of swine, underscoring cattle as the principal reservoir and amplifying host. Bayesian skyline analysis demonstrated a marked decline in global IDV genetic diversity during 2020-2022, coinciding with livestock-movement restrictions imposed during the COVID-19 pandemic. Collectively, these findings indicate that IDV circulation in China is sporadic and geographically localized, dominated by the D/Yamagata/2019 lineage, and shaped by multiple independent incursions rather than a single emergence. Both the incorporation of IDV diagnostics into routine bovine respiratory disease surveillance and cattle-import quarantine programs, and the adoption of a One Health framework to monitor potential human spillover and future viral evolution, were recommend.

Rapid isolation of therapeutic bacteriophages from environmental sources is essential for personalized phage therapy, particularly when appropriate phages are unavailable in existing banks. However, comprehensive characterization of all candidate phages is resource-intensive, especially when plaque morphologies are similar and fail to discriminate between distinct phages. Here, we present an upstream screening approach that utilizes co-culture growth curve analysis to rapidly triage phage isolates during the early isolation process. We extracted seven biologically meaningful features that capture lysis kinetics, lysis efficiency, and post-lysis dynamics from bacterial growth curves and applied unsupervised clustering algorithms for phage discrimination. Validation using T-phages at a multiplicity of infection of 0.01 demonstrated superior clustering performance (Adjusted Rand Index = 0.881 ± 0.057) compared to established metrics including the Virulence Index and Centroid Index. Application to phages isolated from sewage successfully identified all three genomically distinct species present (sampling score = 1.0), enabling targeted selection of representative phages for downstream characterization. This approach reduced candidates requiring detailed analysis by two-thirds (from 21 to 7 isolates) while maintaining complete species coverage, thereby providing an efficient and scalable screening tool that reduces workload for downstream analyses and accelerates discovery of novel therapeutic phages for clinical applications.