Recent observations highlight a notable surge in West Nile Virus (WNV) infections in Europe that can lead to neuroinvasive consequences associated with neurodegeneration, mainly triggered by WNV Non-Structural protein 1 (NS1). During viral replication, various protein-protein interactions take place, allowing viral proteins to interact with host factors. NS1 is actively secreted in the bloodstream by infected cells and is known to affect endothelial permeability and host immune response. Focusing on the recently discovered antimicrobial roles of Amyloid-Beta (Aβ) in the context Central Nervous System (CNS), we connected WNV late pathology to overlapping features encountered in neurodegenerative diseases. In fact, CNS viral infections, or presence of specific viral components, activate glial cells, which in turn increase Aβ expression as an antiviral mechanism, leading to Aβ accumulation and neuronal damage. Considering West Nile neuroinvasive disease (WNND) as a possible complication of WNV infection, we investigated the impact of soluble WNV (s)NS1 on glial and neuronal cells, in 2D and 3D in vitro models. We reported an increased Aβ deposition after WNV sNS1 treatment, particularly of Aβ-142 isoform, and increased glial activation with a subsequent neurotoxicity. These findings underscore the crucial role of sNS1 in CNS-related effects during WNV infection, suggesting a novel pathogenetic role.

The detection of viral DNA is considered crucial in both diagnosis and prognosis. Nowadays, molecular diagnostic approaches represent the most promising tools for the clinical detection of viral infections. This review aims to investigate the most used and promising DNA-based technologies for viral detection, focusing on herpesviruses because of their ability to undergo latent and reactivation cycles, persisting lifelong in the host in association with several diseases. Molecular technologies, such as PCR-based assays, enhance sensitivity and specificity in identifying viral DNA from clinical samples such as blood, cerebrospinal fluid and saliva, indicating PCR and its derivatives as the gold standard methods for herpesvirus detection. In conclusion, this review underscores the need for continuous innovation in diagnostic methodologies to address the complexities of herpesvirus identification in different clinical samples.

Polyomaviruses are a family of small DNA viruses capable of establishing persistent infections, and they can pose significant pathogenic risks in immunocompromised hosts. While traditionally studied in the context of viral reactivation and immune suppression, recent evidence has highlighted the gut microbiota as a critical regulator of host immunity and viral pathogenesis. This review examines the complex interactions between polyomaviruses, the immune system, and intestinal microbiota, emphasizing the role of short-chain fatty acids (SCFAs) in modulating antiviral responses. We explore how dysbiosis may facilitate viral replication, reactivation, and immune escape and also consider how polyomavirus infection can, in turn, alter microbial composition. Particular attention is given to the Firmicutes/Bacteroidetes ratio as a potential biomarker of infection risk and immune status. Therapeutic strategies targeting the microbiota, including prebiotics, probiotics, and fecal microbiota transplantation (FMT), are discussed as innovative adjuncts to immune-based therapies. Understanding these tri-directional interactions may offer new avenues for mitigating disease severity and improving patient outcomes during viral reactivation.