Viruses-Basel最新文献

Citrus yellow vein clearing virus (CYVCV) is the causative agent of the yellow vein clearing disease (YVCD), a worldwide and highly destructive disease in lemon (Citrus lemon) and sour orange trees (C. aurantium). The typical symptoms of vein clearing are believed to be associated with CYVCV infection in citrus, so virus-specific diagnostic systems are currently used to confirm infection. In the present study, virome analysis based on high-throughput sequencing (HTS) on a lemon plant showing YVCD revealed mixed infection of CYVCV, iris domestica betaflexyviridae 1 (IDBV), and hop stunt viroid (HSVd). This multiple infection was confirmed in other two lemon plants with similar symptoms using virus/viroid specific primers. This is the first report of IDBV in lemon. Through molecular characterization and the reconstruction of phylogenetic relationships, a possible origin of the viruses/viroid identified in lemon has been hypothesized. Such mixed infections raise new questions about their role in the expression of YVCD symptoms observed on lemon.

Weight gain has been associated with integrase strand transfer inhibitors (INSTIs) in real-world studies; however, the causality of this relationship is unclear. Thus, we examined the effects of the INSTI, Dolutegravir (DTG), on human adipose cells in vitro and the reversibility of these effects by switching to a protease inhibitor, Darunavir (DRV). We established cultures of human adipose stem cells (ASCs) and newly differentiated adipocytes from individuals without HIV. For adipocytes, cells were exposed to DTG or DRV for 7 days, after which cells were maintained or switched to another ART. Experiments examining ASCs and the effects on adipogenesis initiated exposure during proliferation and continued throughout differentiation. Adipogenic outcomes included triglyceride content, gene expression, and adipokine secretion. Metabolic outcomes included lactate production, lipolysis, and oxygen consumption rates. DTG suppressed the secretion of adiponectin and leptin, and this was reversed following the switch to DRV in adipocytes without the altered expression of adipogenic genes. DTG exposure increased markers of endoplasmic reticulum stress, elevated lactate production, and suppressed oxygen consumption in ASCs. Exposure to DTG during differentiation lowered triglyceride accumulation and adiponectin secretion without altering the expression of adipogenic markers. Thus, DTG exposure resulted in changes in adipocyte function consistent with the progression of metabolically adverse phenotypes, and these effects were reversible.

Respiratory infections represent one of the leading causes of pediatric consultations and hospitalizations in Chile, where rapid etiological identification is essential for clinical decision-making. We evaluated the impact of implementing the BIOFIRE^® SPOTFIRE^® Respiratory (R) Panel in the pediatric Emergency Department of a public referral hospital in Santiago, using a pre-post cross-sectional design comparing two winter periods (July 2023 vs. July 2024). Clinical records, laboratory data, and operational indicators were analyzed to assess changes in diagnostic yield, turnaround time, hospitalizations, discharges, supplementary test requests, and antimicrobial use. A total of 470 patients were included (224 in 2023; 246 in 2024). The etiological detection rate increased from 58.0% to 87.8% after the implementation of Spotfire^® (p < 0.0001), with marked increases in the identification of adenovirus, RSV, rhinovirus/enterovirus, and seasonal coronaviruses. Rapid molecular testing was associated with a significant rise in emergency department discharges (23.7% vs. 57.3%; p < 0.0001) and a reduction in hospitalizations (76.3% vs. 42.7%; p < 0.0001) and readmissions (9.2% vs. 0.5%; p < 0.0001). Requests for complete blood counts, chest X-rays, and antimicrobial prescriptions at discharge also decreased significantly. These effects persisted in key subgroups, including infants and children with comorbidities. In this high-demand winter setting, the BIOFIRE^® SPOTFIRE^® R Panel improved diagnostic performance and supported more efficient and targeted clinical management.

Oncolytic coxsackievirus B3 (oCVB3) strain PD-H has shown potent oncolytic efficacy and a remarkable safety profile in the treatment of colorectal cancer in vivo after intratumoral (i.t.) injection. In this study, we investigated the safety and efficiency of PD-H following intravenous (i.v.) virus administration. When injected i.v. into Balb/C mice bearing subcutaneous Colon-26 tumors, PD-H led to slightly reduced tumor progression and a significant increase in animal survival, but it also caused multi-organ infection and tissue damage. To improve the safety profile of PD-H, we inserted microRNA target sites (miR-TS) of the heart-specific miR-1, pancreas-specific miR-375, liver-specific miR-122, and brain-specific miR-124 or the tumor-suppressor miR-145 into the genome of PD-H and generated the viruses PD-622TS and PD-145TS. Both viruses replicated similarly and induced cytotoxicity comparable to that of PD-H in the colorectal carcinoma cell lines Colon-26 and CT-26Luc. Their replication was inhibited in HEK293T cells transiently transfected with the cognate microRNAs. In vivo, i.v. administration of PD-145TS and PD-622TS to healthy Balb/C mouse resulted in significantly lower viral titers in the organs of mice and led to significantly less-intense pathological alterations compared to PD-H. PD-622TS injected i.v. into Balb/C mice with CT-26Luc-induced peritoneal carcinomatosis did not induce off-target alterations in normal organs, but it failed to induce a therapeutic effect. These data indicate that PD-H or microRNA-regulated PD derivatives exhibit only limited therapeutic efficacy following i.v. injection in colorectal tumor-bearing mice. However, the newly engineered microRNA-regulated PD-H variants demonstrate improved safety profiles.

Exudative epidermitis (EE), caused by Staphylococcus hyicus, represents an issue for swine production, particularly due to antimicrobial resistance. In this project, we isolated bacteriophages using S. hyicus as host and studied them as a potential alternative to antibiotic treatment in Quebec, Canada. Three phages, STAE-4, STAF-3, and STAM-1, were isolated from swine farm samples using a single S. hyicus strain (SC366) as the host. Transmission electron microscopy revealed that all three phages exhibited a siphovirus-like morphology, and RAPD-PCR profiling indicated that the phages were genetically distinct. Whole genome sequencing confirmed these differences and showed that the three phages were closely related to each other, and, more importantly, highly similar to phages previously described as infecting Staphylococcus chromogenes, a species closely related to S. hyicus. Host range analysis confirmed that the three phages preferentially infected the S. chromogenes strains included in the study, exhibiting minimal to no lytic activity against other strains of S. hyicus or Staphylococcus agnetis, another closely related species. The only exception was the host S. hyicus strain SC366, which was effectively infected by all three phages, albeit less efficiently than the most sensitive S. chromogenes strain (SC385). Adsorption tests further supported these observations, showing that phages bound to strain SC366 much more quickly than to SC385, despite the lower lytic activity observed. Taken together, these results highlight that while the phages retain some capacity to infect S. hyicus, their biological properties point to a stronger adaptation to S. chromogenes, indicating that they are not suitable candidates for controlling EE.

Cuba is in a unique situation in which it has a large (220,000 managed colonies) and isolated honey bee population due to a 60+ year ban on the importation of bees. Despite this, the ectoparasitic mite Varroa destructor arrived in 1996, and with it came deformed wing virus (DWV). In 2018, an island-wide survey detected varroa and DWV in 91% of colonies. In this study, we conducted a full-virome analysis on some of these samples, along with additional samples collected in 2021. For the first time, we detected two variants of Lake Sinai Virus and confirmed the absence of the normally widespread black queen cell virus in Cuba. We also detected both DWV-A and DWV-B master variants, with DWV-B being the dominant variant. Interestingly, the DWV-B/A recombinant was also detected, indicating that despite Cuba's isolated nature, the pattern of DWV evolution mirrors that found in the USA and Europe. However, this pattern is not found in neighboring Latin America, China, or Japan, where the DWV-A master variant continues to be dominant. How and why two distinct evolutionary DWV pathways have arisen remain a mystery.

Lamivudine/dolutegravir (3TC/DTG) is an effective and well-tolerated antiretroviral regimen for most people with HIV (PWH) who are virologically suppressed; however, specific clinical characteristics, such as prior hepatitis B virus (HBV) exposure or archived resistance-associated mutations (RAMs), may influence the risk of virological failure (VF). We conducted a retrospective, monocentric cohort study to evaluate the incidence and predictors of VF among PWH who switched to 3TC/DTG after achieving virological suppression (HIV-RNA < 50 copies/mL). A total of 188 PWH were included. Over 5082 patient-years of follow-up (PYFU), 8 individuals (4.3%) experienced VF, corresponding to an incidence rate of 1.45 per 1000 PYFU. The cumulative probabilities of VF at 1, 2, 3, 4, and 5 years were 0.6%, 2.7%, 2.7%, 4.2%, and 22.3%, respectively. In exploratory multivariable analyses, anti-HBc positivity was associated with an increased risk of VF (adjusted hazard ratio [aHR] 4.80, 95% CI 1.03-22.43; p = 0.046). After adjustment for age and sex, individuals with anti-HBc positivity who had switched from a tenofovir-containing regimen showed the highest risk of VF compared with anti-HBc-negative individuals without prior tenofovir exposure (aHR 15.06, 95% CI 1.40-161.38; p = 0.025). Given the limited number of virological events, these findings should be interpreted with caution. Nevertheless, they suggest that prior HBV exposure, particularly in the context of tenofovir discontinuation, may represent a clinically relevant factor when considering simplification to 3TC/DTG.

The first major HIV outbreak in the Eastern Europe and Central Asia (EECA) region was registered. Phylogeographic analysis revealed that the main exporters of the virus were Donetsk and Lugansk, from which most migration events occurred, and the predominant genetic variant in Donetsk was subtype A. However, despite a relatively high level of understanding of HIV genetic diversity, data on resistance mutations remain limited. The aim of this study is to assess HIV genetic diversity and drug resistance in Donetsk, Luhansk and Zaporizhzhia regions. A comprehensive examination was conducted, encompassing 392 sequences covering the integrase-coding region of the HIV-1 pol gene. Subtyping was achieved through various programs, including COMET, the Stanford Database, BLAST and REGA. The study also involved phylogenetic analysis to clarify HIV genovariants. The profiles and levels of drug resistance were determined. The overall prevalence of drug resistance mutations to the integrase strand transfer inhibitors (INSTIs) among the studied patients was 3.6% (95% CI, 1.7-5.4%). The most commonly detected major DRMs for INSTIs were G140R (4, 28.6%) and Y143R (3, 21.4%), followed by R263K (2, 14.3%), G140RG (2, 14.3%), Y143YS (2, 14.3%), Y143YC (1, 7.1%) and Q148QR (1, 7.1%). A high-level resistance was observed for RAL-8/14 (57.1%), CAB-6/14 (42.9%) and EVG-2/14 (14.3%). The results presented are part of a further larger study and are preliminary. The results of this study suggest a moderate HIV-1 resistance situation in the Donetsk, Luhansk and Zaporizhzhia regions, but require further monitoring.

HTLV-1 and HIV-1 represent biologically significant, structurally close, and equally problematic yet divergent human retroviruses. Although both infect CD4+ T cells and share similar structural elements, they differ markedly in genomic stability, transmission dynamics, clinical progression, and, most importantly, their transcriptional regulatory mechanisms. HTLV-1, an ancient virus with a limited global burden, often remains asymptomatic for decades before potentially causing ATL or HAM/TSP. Conversely, HIV-1, a relatively recent zoonotic transmission, undergoes rapid replication, exhibits high genetic diversity, and causes progressive immunodeficiency unless controlled by antiretroviral therapy (ART). At the molecular level, HTLV-1 maintains proviral latency through a balanced bidirectional transcription of regulatory genes (e.g., Tax and HBZ) that manipulate host transcription and immune evasion pathways, facilitating persistence and oncogenesis. HBZ and Tax were shown to contribute to driving the progressive acquisition of Treg-like and HLA class II phenotype in chronically activated CD4+ T-cells, promoting tolerogenic antigen presentation and immune evasion in ATL cells. This well-controlled differential expression of HTLV-1 regulatory genes is attributed to multiple intragenic virus regulatory mechanisms, which will be discussed in this review. In contrast, HIV-1 transcription is driven by a tightly regulated 5' LTR promoter involving host factors such as NF-κB, Sp1, AP-1, and NFAT, among others, with strong influence imposed by the landscape of the provirus integration site, playing a pivotal role in latency and reactivation. The distinct regulatory circuitry of each virus suggests a key difference in their essential regulation, with HTLV-1 primarily relying on intragenic mechanisms, while HIV-1 relies more heavily on interactions with the surrounding host environment to control its expression. This difference underscores unique therapeutic challenges in managing viral latency, persistence, and pathogenesis.

Studying the incidence of Kaposi sarcoma in relation to key variables can guide targeted research and subtype-specific clinical interventions. We reviewed the records of all patients who visited our hospital's dermatology outpatient clinic, and patients who were clinically and histopathologically diagnosed with Kaposi sarcoma were included in the study. The age, gender, lesion location, anti-HIV test results, and comorbidities of the patients were recorded. Thirty-three patients with Kaposi sarcoma were identified. The male/female ratio was 2.7:1. The Kaposi sarcoma lesions were statistically significantly more prevalent in the lower extremities of HIV-negative patients (p = 0.005). Receiver operating characteristic (ROC) curve analysis identified 59 years as the optimal age cutoff for distinguishing between HIV-positive and HIV-negative patients. Anti-HIV positivity was significantly higher in individuals aged 59 and younger compared to those aged 60 and older (p < 0.001). To the best of our knowledge, this is the first study to demonstrate a statistically significant higher prevalence of lower extremity lesions among HIV-negative patients and to identify 59 years as the optimal age cutoff for distinguishing between HIV-positive and HIV-negative Kaposi sarcoma patients using ROC curve analysis. The age-related patterns observed in this study warrant further investigation.