Cystic fibrosis (CF), an autosomal-recessive genetic disorder, is caused by mutations in the CFTR gene, which encodes for a membrane anion channel expressed on multiple organs, with major impact on the airways. The impaired ion transport leads to thickened mucus secretions, which in turn can cause pancreatic insufficiency, sinusitis, infertility and, particularly, chronic pulmonary infections. While bacterial colonization of the airways has been extensively studied, increasing evidence highlights the significant, yet underappreciated, role of respiratory viruses in exacerbating lung disease in people with CF (pwCF). This review provides a comprehensive overview of the pathogenesis, epidemiology, and clinical impact of key respiratory viruses, including respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza viruses, parainfluenza viruses, coronaviruses, and emerging pathogens such as human bocavirus, as well as relevant non-respiratory viruses, such as Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and hepatitis viruses. Viral infections in pwCF are associated, particularly in pediatric patients, with increased respiratory symptoms, higher hospitalization rate and long-term decline in lung function. Despite a similar incidence of viral infections to non-CF individuals, pwCF often exhibit more severe clinical outcomes, except for SARS-CoV-2 infection, which shows an incidence and severity unexpectedly attenuated in this cohort. Moreover, while CFTR modulators have dramatically improved clinical outcomes in pwCF, their effects on antiviral immunity remain poorly understood and are an area of active investigation. Elucidating virus-host interactions and the impact of CFTR restoration in this context is essential for optimizing preventive and therapeutic strategies against viral infections in CF.

Combined antiretroviral therapy (cART) has deeply changed the approach to HIV disease treatment. cART tackles HIV replication and improves the life expectancy of HIV-infected people. Notwithstanding the effectiveness of cART in HIV infection control, several observations have determined that 15–50% of HIV-infected people display HIV-associated neurocognitive disorders (HAND) even under long-term viral suppression. Persistent production of the viral proteins Tat and gp120 by central nervous system reservoirs drives chronic neurotoxicity due to their remarkable extracellular stability and efficient uptake by neurons and glial cells. In this review, we will discuss current evidence on the molecular mechanisms by which extracellular Tat and gp120 orchestrate neurodegeneration. Four principal interconnected pathways emerge: (i) mitochondrial dysfunction; (ii) synaptodendritic injury; (iii) chronic neuroinflammation; and (iv) crosstalk with Alzheimer’s disease (AD) pathways. Converging data achieved from in vitro models, Tat and gp120-transgenic mice, post-mortem tissue, and cerebrospinal fluid (CSF) biomarkers indicate that these viral proteins contribute to frontostriatal atrophy and hybrid HAND-AD phenotypes increasingly observed in aging HIV patients. Understanding these mechanisms highlights the need for adjunctive neuroprotective strategies targeting CXCR4/CCR5 signaling, mitochondrial quality control, inflammatory pathways, and Aβ/Tau homeostasis derangement and supports the integration of multimodal neuroimaging and CSF proteomics in future longitudinal studies aimed at improving diagnosis and therapeutic development.

Cystic fibrosis (CF) is characterized by chronic airway inflammation, yet clinical observations have revealed more favorable COVID-19 outcomes than originally predicted. Several studies demonstrated a significant decrease of SARS-CoV-2 replication in CF-mutated bronchial cells suggesting that CFTR dysfunction may interfere with viral replication, though the underlying mechanisms remain unclear. To elucidate these mechanisms we performed transcriptomic profiling of SARS-CoV-2-infected bronchial epithelial cells with wild-type (WT) or mutated CFTR, using both immortalized and primary airway models. RNA-seq was performed on WT and CF cellular models before and at 24, 48, and 72-hours post-infection. The differentially expressed genes (DEGs) were defined as genes with a log2 fold change>1 between groups (p<0.05) and significant DEGs were subjected to Gene Ontology and KEGG enrichment analysis (p<0.05). Our results reveal that CFTR deficiency impairs SARS-CoV-2 replication not by altering receptor availability (e.g., ACE2, TMPRSS2), but through widespread intracellular remodeling defects. CF cells failed to activate key antiviral and inflammatory responses, including interferon signaling, AP-1 transcriptional complex, and IL-6-mediated pathways. Furthermore, they exhibited defective unfolded protein response, altered calcium signaling, and disrupted ER-mitochondrial communication. Crucially, pH dysregulation and impaired expression of V-ATPase subunits and autophagy-related genes hindered vesicle acidification, double-membrane vesicle formation, and viral assembly. These intrinsic alterations also blunted virus-induced senescence programs. Collectively, our findings indicate that CF cellular environment is intrinsically unfavorable to SARS-CoV-2, limiting its replication and propagation. This study provides a mechanistic basis for the reduced viral burden observed in CF and highlights intracellular pH regulation and organelle homeostasis as potential therapeutic targets against SARS-CoV-2 infection.

HIV-associated neurocognitive disorders (HAND) persist despite effective antiretroviral therapy, indicating that chronic neuroimmune dysfunction extends beyond active viral replication. Among HIV-1-derived factors, the viral proteins Tat and gp120 are contributors to sustained brain inflammation. Nevertheless, their comparative impact in genetically vulnerable neural environments remains unclear. Here, we performed a secondary transcriptomic analysis of publicly available RNA-seq data derived from the striatal tissue of hSNCAA53T Gba1+/L444P mice, a model combining α-synuclein overexpression with Gba1-associated lysosomal impairment, following unilateral intrastriatal injection of Tat or gp120. Both proteins induced robust transcriptional remodelling selectively in the injected striatum. Tat primarily elicited a broad inflammatory amplification programme encompassing innate immune sensing, chemokine recruitment, adaptive immune engagement, and loss of homeostatic support. gp120 preferentially activated antigen presentation, complement, oxidative stress, and lysosomal–phagocytic effector pathways consistent with immune-mediated synaptic stress. Despite these distinct profiles, Tat and gp120 converged on a shared microglia-centred effector core. Contralateral striatal tissue was analyzed as distal non-injected tissue to explore the spatial distribution of transcriptional responses and minimal and protein-specific effects were reported. These findings provide a mechanistic framework for HAND heterogeneity and suggest that HIV protein-driven neuroimmune transcriptional programmes may create a molecular environment compatible with increased neurodegenerative vulnerability in lysosome-compromised, α-synuclein-sensitized brains.

Omsk hemorrhagic fever virus (OHFV) is the etiological agent of a poorly studied acute viral disease, causing several epidemic waves observed in the western Siberia regions of Omsk, Kurgan, Novosibirsk, and Tyumen. OHFV is a flavivirus and shares structural and morphological features with tick-borne encephalitis (TBE) complex viruses. The disease’s symptoms show high variability, from flu-like symptoms, hyperesthesia, and petechial rush in the upper body to high fever and hemorrhagic manifestations, with a fatality rate of about 1%. The real number of OHFV-infected people is still unknown due to the difficulties in diagnosis and the presence of asymptomatic patients that lead to an underestimation of the total cases. Little is known about the viral infection dynamics at the molecular and cellular levels, the viral involvement in immune escape, cellular pathways alteration, or metabolic influence. It is noteworthy that no clinical trials have currently been performed for effective and specific drug treatments. In this review, we will give an overview of OHFV interactions with humans and animals, diagnostic tools, and drug treatments. We aim to highlight the importance of a frequently undiagnosed or misdiagnosed viral infection that might also even cause severe clinical manifestations such as meningitis and hemorrhage, in order to point out the need to develop new research studies, new diagnostic tools, and new treatments for OHFV.

Background: The continuous emergence of SARS-CoV-2 variants represents a major public health concern. Next-generation sequencing (NGS) enables genomic surveillance, facilitating the detection and monitoring of mutations that impact viral evolution. Methods: In this study, full-length SARS-CoV-2 genomes were analyzed between February 2022 and March 2024 as part of routine genomic surveillance conducted in Verona, Italy. Mutations in the envelope (E), membrane (M), and nucleocapsid (N) structural proteins were investigated. Only substitutions with a total prevalence of greater than 1% in the study dataset were considered. Results: A total of 178 mutations were identified across the three proteins (E: 16; M: 33; N: 129), of which 18 met the inclusion threshold (E: 3; M: 5; N: 10). Mutations were classified according to temporal dynamics as fixed, emerging, or transient. Throughout the study period, fixed mutations were consistently prevalent, emerging mutations appeared later but persisted with an ascending trend, while transient mutations displayed a single frequency peak before disappearing. Several mutations were reported with potential structural or functional relevance based on the existing literature, while others remain of unknown significance. Conclusions: The mutational patterns detected in this study broadly reflect global evolutionary trends of SARS-CoV-2. These findings emphasize the importance of continued genomic surveillance and underline the need for integrated experimental approaches to clarify the biological and epidemiological impact of poorly characterized mutations.

The repeated occurrence of SARS-CoV-2 variants, largely driven by virus–host interactions, was and will remain a public health concern. Spike protein mutations shaped viral infectivity, transmissibility, and immune escape. From February 2022 to April 2024, a local genomic surveillance program in Verona, Italy, was conducted on 1333 SARS-CoV-2-positive nasopharyngeal swabs via next generation full-length genome sequencing. Spike protein mutations were classified based on their prevalence over time. Mutations were grouped into five categories: fixed, emerging, fading, transient, and divergent. Notably, some divergent mutations displayed a “Lazarus effect,” disappearing and later reappearing in new lineages, indicating potential adaptive advantages in specific genomic contexts. This two-year surveillance study highlights the dynamic nature of spike protein mutations and their role in SARS-CoV-2 evolution. The findings underscore the need for ongoing mutation-focused genomic monitoring to detect early signals of variant emergence, especially among mutations previously considered disadvantageous. Such efforts are critical for driving public health responses and guiding future vaccine and therapeutic strategies.

Magnusiomyces clavatus is an emerging opportunistic fungal pathogen associated with severe systemic infections in immunocompromised patients, mostly among those suffering from hematological malignancies. Despite the increasing clinical significance, genomic data for M. clavatus remain limited. In this study, we report the first chromosomal-level genome assembly of M. clavatus using hybrid sequencing with Illumina and Oxford Nanopore Technologies. Three clinical isolates obtained from ICU patients in Verona (Italy) were sequenced and analyzed. The M. clavatus genome was resolved into 4 nuclear chromosomes and 1 circular mitochondrial genome, with a total length of 17.6 Mb and with 4,065 predicted protein-coding genes. Comparative analyses revealed structural differences from its closely related species M. capitatus. Phylogenetic analysis of 40 strains assembled on the resolved genome identified a novel clade (D), distinct from the previously described clades A, B, and C. All isolates exhibited intrinsic resistance to echinocandins and fluconazole. Genetic analysis identified conserved mutations in the FKS1 hotspot region encoding 1,3-β-glucan synthase, mirroring resistance-associated substitutions in M. capitatus. Additionally, a putative cyp51 homolog was identified as a likely contributor to azole resistance, suggesting conserved resistance mechanisms across Magnusiomyces species. This study discloses a new chromosomal-level assembly for M. clavatus, providing a significant genomic framework. This resource could enhance the accuracy of diagnostic methods, enabling comparative genomics with closely related fungi and facilitating a deeper investigation into the mechanisms of antifungal resistance and pathogenicity of this rare but increasingly reported pathogen.

Beyond the well-documented oncogenic role of Epstein–Barr virus (EBV), a growing body of evidence implicates other herpesviruses, notably Kaposi’s sarcoma-associated herpesvirus and human herpesvirus (HHV) 6, in the pathogenesis of specific lymphoma subtypes. HHV-7 has also been detected in lymphoma tissues, though its contribution remains less defined. This review systematically examines the epidemiological associations and experimental insights linking these non-EBV herpesviruses to lymphoid malignancies. The discussion delves into the molecular mechanisms through which virally encoded molecules influence critical cellular programs, including the modulation of immune responses, epigenetic reprogramming, and the induction of chronic inflammation. We also review how these viruses hijack multilayered cellular networks, such as nuclear factor kappa B and Janus Kinase/signal transducer and activator of transcription signaling, and reprogram cellular metabolism to support malignant growth. A critical re-evaluation of the evidence for HHV-7 positions it as a putative cofactor in lymphomagenesis, contingent on host immunosuppression, rather than a primary oncogenic driver, highlighting the current absence of proven causality and robust in vivo models. Furthermore, this review provides a structured overview of the clinical implications of these viral associations. We also outline the established diagnostic tools, such as immunohistochemistry and quantitative protein-coupled receptor (PCR), and emerging technologies such as droplet digital PCR and liquid biopsy that hold considerable promise to refine disease monitoring. Meanwhile, we delineate standard-of-care treatments for virus-associated lymphomas from promising investigational approaches, including virus-targeted interventions and novel immunotherapies, offering a framework for both current clinical practice and future research.

We investigated the activity of cefiderocol/β-lactamase inhibitor combinations against clinical strains with different susceptibility profiles to cefiderocol to explore the potentiality of antibiotic combinations as a strategy to contain the major public health problem of multidrug-resistant (MDR) pathogens. Specifically, we evaluated the synergistic activity of cefiderocol with avibactam, sulbactam, or tazobactam on three of the most “Critical Priority” group of MDR bacteria (carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii). Clinical isolates were genomically characterized by Illumina iSeq 100. The synergy test was conducted with time-kill curve assays. Specifically, cefiderocol/avibactam, /sulbactam, or /tazobactam combinations were analyzed. Synergism was assigned if bacterial grow reduction reached 2 log10 CFU/mL. We reported the high antimicrobial activity of the cefiderocol/sulbactam combination against carbapenem-resistant Enterobacterales, P. aeruginosa, and A. baumannii; of the cefiderocol/avibactam combination against carbapenem-resistant Enterobacterales; and of the cefiderocol/tazobactam combination against carbapenem-resistant Enterobacterales and P. aeruginosa. Our results demonstrate that all β-lactamase inhibitors (BLIs) tested are able to enhance cefiderocol antimicrobial activity, also against cefiderocol-resistant isolates. The cefiderocol/sulbactam combination emerges as the most promising combination, proving to highly enhance cefiderocol activity in all the analyzed carbapenem-resistant Gram-negative isolates, whereas the Cefiderocol/tazobactam combination resulted in being active only against carbapenem-resistant Enterobacterales and P. aeruginosa, and cefiderocol/avibactam was only active against carbapenem-resistant Enterobacterales.

The emergence of antimicrobial resistance represents a serious threat to public health and for infections due to multidrug-resistant (MDR) microorganisms, representing one of the most important causes of death worldwide. The renewal of old antimicrobials, such as colistin, has been proposed as a valuable therapeutic alternative to the emergence of the MDR microorganisms. Although colistin is well known to present several adverse toxic effects, its usage in clinical practice has been reconsidered due to its broad spectrum of activity against Gram-negative (GN) bacteria and its important role of “last resort” agent against MDR-GN. Despite the revolutionary perspective of treatment with this old antimicrobial molecule, many questions remain open regarding the emergence of novel phenotypic traits of resistance and the optimal usage of the colistin in clinical practice. In last years, several forward steps have been made in the understanding of the resistance determinants, clinical usage, and pharmacological dosage of this molecule; however, different points regarding the role of colistin in clinical practice and the optimal pharmacokinetic/pharmacodynamic targets are not yet well defined. In this review, we summarize the mode of action, the emerging resistance determinants, and its optimal administration in the treatment of infections that are difficult to treat due to MDR Gram-negative bacteria.

Here, we characterize the complete genome sequence of Escherichia coli isolated from a newborn affected by bacterial meningitis in Italy. Genome of E. coli strain 1455 harbored a circular chromosome and two plasmids of 167.740-bp and 4.073-bp in length, respectively. E. coli 1455 belonged to the ST3, serotype O17:H18 and carried different determinants including resistance to B-lactams, tetracyclines, and quinolones. In addition, genome of E. coli strain 1455 harbored 5 integrated pro-phage regions mainly located in the chromosome, while most of the virulence factors associated to the invasiveness and clinical severity and different antimicrobial resistance determinants (blaTEM-1, tet(A) and qnrS1) were located in the 167-Kb plasmid. Taken together, our findings suggest a possible widespread of a virulence factors-carrying plasmid worldwide and highlight the importance of genomic characterization in the diffusion of public health threats.

Carbapenemase-producing Enterobacteriales (CPE) represent an emerging threat for global public health and a serious problem for clinicians due to the limited available treatment options. The emergence of CPE has been recently described worldwide by describing different antimicrobial mechanisms. Here, we describe a CPE carrying dual-carbapenemase isolated in Italy and we provide a deep characterization of the antimicrobial resistance genes, virulence-factors and prophage regions within the genome.

The onset of the SARS-CoV-2 virus led to the appearance of a devastating pandemic, which once again demonstrated the practical importance of virology [...]

The availability of new technologies for deep sequencing, including next-generation sequencing (NGS), allows for the detection of viral genome variations. The epidemiological determination of SARS-CoV-2 viral genome changes during the pandemic waves displayed the genome evolution and subsequent onset of variants over time. These variants were often associated with a different impact on viral transmission and disease severity. We investigated, in a retrospective study, the trend of SARS-CoV-2-positive samples collected from the start of the Italian pandemic (January 2020) to June 2023. In addition, viral RNAs extracted from 938 nasopharyngeal swab samples were analyzed using NGS between February 2022 and June 2023. Sequences were analyzed with bioinformatic tools to identify lineages and mutations and for phylogenetic studies. Six pandemic waves were detected. In our samples, we predominantly detected BA.2, BQ.1, BA.5.1, BA.5.2, and, more recently, XBB.1 and its subvariants. The data describe the SARS-CoV-2 genome evolution involved in viral interactions with the host and the dynamics of specific genome mutations and deletions.

Flaviviruses cause numerous pathologies in humans across a broad clinical spectrum with potentially severe clinical manifestations, including hemorrhagic and neurological disorders. Among human flaviviruses, some viral proteins show high conservation and are good candidates as targets for drug design. From an epidemiological point of view, flaviviruses cause more than 400 million cases of infection worldwide each year. In particular, the Yellow Fever, dengue, West Nile, and Zika viruses have high morbidity and mortality-about an estimated 20,000 deaths per year. As they depend on human vectors, they have expanded their geographical range in recent years due to altered climatic and social conditions. Despite these epidemiological and clinical premises, there are limited antiviral treatments for these infections. In this review, we describe the major compounds that are currently under evaluation for the treatment of flavivirus infections and the challenges faced during clinical trials, outlining their mechanisms of action in order to present an overview of ongoing studies. According to our review, the absence of approved antivirals for flaviviruses led to in vitro and in vivo experiments aimed at identifying compounds that can interfere with one or more viral cycle steps. Still, the currently unavailability of approved antivirals poses a significant public health issue.

SARS-CoV-2 infection is mainly detected by multiplex real-time RT-PCR from upper respiratory specimens, which is considered the gold-standard technique for SARS-CoV-2 infection diagnosis. A nasopharyngeal (NP) swab represents the clinical sample of choice, but NP swabbing can be uncomfortable to the patients, especially for pediatric-age participants, requires trained healthcare personnel, and may generate an aerosol, increasing the intrinsic exposure risk of healthcare workers. The objective of this study was to compare paired NP and saliva samples (SS) collected from pediatric patients to evaluate whether the saliva collection procedure may be considered a valuable alternative to the classical NP swab (NPS) sampling in children. In this study, we describe a SARS-CoV-2 multiplex real-time RT-PCR protocol for SS, comparing the results with the paired NPS specimens from 256 pediatric patients (mean age 4.24 ± 4.40 years) admitted to the hospital emergency room of Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, and randomly enrolled between September 2020 and December 2020. The saliva sampling demonstrated consistent results when compared to NPS use. The SARS-CoV-2 genome was detected in 16 out of 256 (6.25%) NP samples, among which 13 (5.07%) were positive even when paired SS were analyzed. Moreover, SARS-CoV-2-negative NPS and SS were consistent, and the overall concordances between NPS and SS were detected in 253 out of 256 samples (98.83%). Our results suggest that saliva samples may be considered a valuable alternative to NPS for SARS-CoV-2 direct diagnosis with multiplex real-time RT-PCR in pediatric patients.

Several reports have indicated that SARS-CoV-2 infection displays unexpected mild clinical manifestations in people with cystic fibrosis (pwCF), suggesting that CFTR expression and function may be involved in the SARS-CoV-2 life cycle. To evaluate the possible association of CFTR activity with SARS-CoV-2 replication, we tested the antiviral activity of two well-known CFTR inhibitors (IOWH-032 and PPQ-102) in wild type (WT)-CFTR bronchial cells. SARS-CoV-2 replication was inhibited by IOWH-032 treatment, with an IC50 of 4.52 μM, and by PPQ-102, with an IC50 of 15.92 μM. We confirmed this antiviral effect on primary cells (MucilAirTM wt-CFTR) using 10 μM IOWH-032. According to our results, CFTR inhibition can effectively tackle SARS-CoV-2 infection, suggesting that CFTR expression and function might play an important role in SARS-CoV-2 replication, revealing new perspectives on the mechanisms governing SARS-CoV-2 infection in both normal and CF individuals, as well as leading to potential novel treatments.