Parvovirus B19 (B19V) is a human pathogen belonging to the Parvoviridae family. It is widely diffused in the population and responsible for a wide range of diseases, diverse in pathogenetic mechanisms, clinical course, and severity. B19V infects and replicates in erythroid progenitor cells (EPCs) in the bone marrow leading to their apoptosis. Moreover, it can also infect, in an abortive manner, a wide set of different cell types, normally non-permissive, and modify their normal physiology. Differences in the characteristics of virus–cell interaction may translate into different pathogenetic mechanisms and clinical outcomes. Joint involvement is a typical manifestation of B19V infection in adults. Moreover, several reports suggest, that B19V could be involved in the pathogenesis of some autoimmune rheumatologic diseases such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), or vasculitis. This review provides basic information on the B19 virus, highlights characteristics of viral infection in permissive and non-permissive systems, and focuses on recent findings concerning the pathogenic role of B19V in rheumatologic diseases.
Fibrosis is the most characteristic pathological hallmark of SSc, a connective tissue disease characterized by vascular and immunological abnormalities, inflammation and enhanced extracellular matrix production, leading to progressive fibrosis of skin and internal organs. We previously demonstrated that parvovirus B19 (B19V) can infect normal human dermal fibroblasts (NHDFs) and that B19V persists in SSc fibroblasts. In this study, we investigated whether parvovirus B19V is able to activate in vitro NHDFs and to induce in these cells some phenotypic features similar to that observed in the SSc fibroblasts. We preliminarily analysed the time course of B19V infection in cultured NHDFs, then we investigated the ability of B19V to induce cell migration, invasive phenotype and mRNA expression of some profibrotic and/or proinflammatory genes. We confirmed our previous findings that B19V infects NHDFs, but the infection is not productive. After incubation with B19V, NHDFs showed a significant increase of both migration and invasiveness, along with mRNA expression of different profibrotic genes (α-SMA, EDN-1, IL-6, TGF-β1 receptors 1 and 2, Col1α2), some genes associated with inflammasome platform (AIM2, IFI16, IL-1β, CASP-1) and genes for metalloprotease (MMP 2, 9 and 12). These data suggest that B19V can activate dermal fibroblasts and may have a role in the pathogenesis of fibrosis. B19V-induced fibroblast migration and invasiveness could be due to the B19V-associated MMP9 overexpression and activation. Moreover, the up-regulation of MMP12, typical of SSc, could link the B19V infection of fibroblasts to the anti-angiogenic process.
Several reports have proposed that the viral load of torque teno virus (TTV) in plasma is a biomarker of immune function in solid organ transplantation (SOT) and in allogeneic hematopoietic stem ce...
Background: West Nile virus (WNV) is a mosquito-borne RNA virus, with birds as reservoirs and humans as incidental hosts. WNV often causes asymptomatic infections, but severe neuroinvasive disease occurs in fewer than 1% of human cases. Recent climatic changes and occupational exposure have increased its spread, particularly in Southern Italy. This study aimed to assess WNV seroprevalence and occupational risks among outdoor workers to guide targeted public health interventions. Methods: This cross-sectional study was conducted in the Apulia region, southeastern Italy, from November 2023 to April 2024. Participants completed a detailed questionnaire on socio-demographics, occupational exposure, travel history, and health symptoms. Blood samples were analyzed using enzyme-linked immunosorbent assay (ELISA) and neutralization assays to detect WNV-specific antibodies. Results: 250 outdoor workers in southeastern Italy were recruited, including agricultural workers, veterinarians, forestry workers, and livestock breeders. The latter showed the highest WNV prevalence at 6.5%. Protective measures such as repellent use (β = −0.145, OR = 0.95, p = 0.019) and personal protective equipment (PPE) usage (β = −0.12, OR = 0.94, p = 0.04) significantly reduced the likelihood of WNV infection. Conclusions: The study highlights the significant occupational risk posed by WNV to outdoor workers involved in livestock breeding in Southern Italy, likely due to their frequent exposure to mosquito-prone environments. Tailored public health strategies and education programs are needed to protect high-risk outdoor workers from WNV, amidst the backdrop of changing climatic conditions that favor increased transmission.
Zika virus (ZIKV) is a positive-sense single-stranded virus member of the Flaviviridae family. Among other arboviruses, ZIKV can cause neurological disorders such as Guillain Barré syndrome, and it can have congenital neurological manifestations and affect fertility. ZIKV nonstructural protein 5 (NS5) is essential for viral replication and limiting host immune detection. Herein, we performed virtual screening to identify novel small-molecule inhibitors of the ZIKV NS5 methyltransferase (MTase) domain. Compounds were tested against the MTases of both ZIKV and DENV, demonstrating good inhibitory activities against ZIKV MTase. Extensive molecular dynamic studies conducted on the series led us to identify other derivatives with improved activity against the MTase and limiting ZIKV infection with an increased selectivity index. Preliminary pharmacokinetic parameters have been determined, revealing excellent stability over time. Preliminary in vivo toxicity studies demonstrated that the hit compound 17 is well tolerated after acute administration. Our results provide the basis for further optimization studies on novel non-nucleoside MTase inhibitors.
Although in humans West Nile virus is mainly the cause of mild or sub-clinical infections, in some cases a neuroinvasive disease may occur predominantly in the elderly. In Italy, several cases of West Nile virus infection are reported every year. Tuscany was the first Italian region where the virus was identified; however, to date only two cases of infection have been reported in humans. This study aimed at evaluating the prevalence of antibodies against West Nile virus in the area of Siena Province to estimate the recent circulation of the virus. Human serum samples collected in Siena between 2016 and 2019 were tested for the presence of antibodies against West Nile virus by ELISA. ELISA positive samples were further evaluated using immunofluorescence, micro neutralization, and plaque reduction neutralization assays. In total, 1.9% (95% CI 1.2–3.1) and 1.4% (95% CI 0.8–2.4) of samples collected in 2016–2017 were positive by ELISA and immunofluorescence assay, respectively. Neutralizing antibodies were found in 0.7% (95% CI 0.3–1.5) of samples. Additionally, 0.9% (95% CI 0.4–1.7) and 0.65% (95% CI 0.3–1.45) of samples collected in 2018–2019 were positive by ELISA and immunofluorescence assay, respectively. The prevalence of neutralizing antibodies was 0.5% (95% CI 0.2–1.3). Although no human cases of West Nile infection were reported in the area between 2016 and 2019 and virus prevalence in the area of Siena Province was as low as less than 1%, the active asymptomatic circulation confirms the potential concern of this emergent virus for human health.