High-risk HPV oncoproteins E6 and E7 and their interplay with the innate immune response: Uncovering mechanisms of immune evasion and therapeutic prospects.

Human papillomaviruses (HPVs) are double-stranded DNA (dsDNA) tumor viruses causally associated with 5% of human cancers, comprising both anogenital and upper aerodigestive tract carcinomas. Despite the availability of prophylactic vaccines, HPVs continue to pose a significant global health challenge, primarily due to inadequate vaccine access and coverage. These viruses can establish persistent infections by evading both the intrinsic defenses of infected tissues and the extrinsic defenses provided by professional innate immune cells. Crucial for their evasion strategies is their unique intraepithelial life cycle, which effectively shields them from host detection. Thus, strategies aimed at reactivating the innate immune response within infected or transformed epithelial cells, particularly through the production of type I interferons (IFNs) and lymphocyte-recruiting chemokines, are considered viable solutions to counteract the adverse effects of persistent infections by these oncogenic viruses. This review focuses on the complex interplay between the high-risk HPV oncoproteins E6 and E7 and the innate immune response in epithelial cells and HPV-associated cancers. In particular, it details the molecular mechanisms by which E6 and E7 modulate the innate immune response, highlighting significant progress in our comprehension of these processes. It also examines forward-looking strategies that exploit the innate immune system to ameliorate existing anticancer therapies, thereby providing crucial insights into future therapeutic developments.

Antibiotic resistance and pathogen spreading in a wastewater treatment plant designed for wastewater reuse.

Climate change significantly contributes to water scarcity in various regions worldwide. While wastewater reuse is a crucial strategy for mitigating water scarcity, it also carries potential risks for human health due to the presence of pathogenic and antibiotic resistant bacteria (ARB). Antibiotic resistance represents a Public Health concern and, according to the global action plan on antimicrobial resistance, wastewater role in selecting and spreading ARB must be monitored. Our aim was to assess the occurrence of ARB, antibiotic resistance genes (ARGs), and potential pathogenic bacteria throughout a wastewater treatment plant (WWTP) designed for water reuse. Furthermore, we aimed to evaluate potential association between ARB and ARGs with antibiotics and heavy metals. The results obtained revealed the presence of ARB, ARGs and pathogenic bacteria at every stage of the WWTP. Notably, the most prevalent ARB and ARG were sulfamethoxazole-resistant bacteria (up to 7.20 log CFU mL-1) and sulII gene (up to 5.91 log gene copies mL-1), respectively. The dominant pathogenic bacteria included Arcobacter, Flavobacterium and Aeromonas. Although the abundance of these elements significantly decreased during treatment (influent vs. effluent, p < 0.05), they were still present in the effluent designated for reuse. Additionally, significant correlations were observed between heavy metal concentrations (copper, nickel and selenium) and antibiotic resistance elements (ampicillin-resistant bacteria, tetracycline-resistant bacteria, ARB total abundance and sulII) (p < 0.05). These results underscore the importance of monitoring the role of WWTP in spreading antibiotic resistance, in line with the One Health approach. Additionally, our findings suggest the need of interventions to reduce human health risks associated with the reuse of wastewater for agricultural purposes.