The human cytomegalovirus (HCMV) UL24 and UL43 are tegument proteins that have recently been shown to interact with each other in a yeast two-hybrid system. By their overexpression in MRC5 cells, we demonstrate that these viral proteins interact with several important host proteins, especially Dicer and trans-activation response RNA binding protein. As these hots proteins are involved in regulating the production of cellular micro-RNAs, the cytomegalovirus (CMV) proteins could interfere with their actions to favor viral replication directly or through an immune escape mechanism. Double knockout of UL24 and UL43 does not show a remarkable effect on CMV entry or replication, but it significantly downregulates the expression of CMV-encoded miR-UL59, which is thought to regulate the expression of a downstream target UL16 binding protein 1 (ULBP1). Interestingly, the double knockout increases the expression of the ULBP1 recognized by the NKG2D activating receptor of natural killer cells. This study investigates the potential role of several proteins encoded by HCMV in regulating the host cellular environment to favor escape from immunity, and it also provides some basis for the future development of RNA-targeted small molecules to control HCMV infection.

The bioactive components of honeybee venom (HBV) have displayed broad evolutionary antiviral activity in animal models; however, there is limited evidence for the efficacy, indications, or side effects of the use of HBV in humans. We performed a systematic review and meta-analysis of the available preclinical and clinical evidence systematically assessing the antiviral efficacy and safety of HBV. A comprehensive search strategy for all studies reporting HBV in relation to direct-acting antiviral effects was performed through electronic databases from their inception up to October 2025. A total of 32 articles were identified for quantitative synthesis, with some included under meta-analysis. Although majority of the studies show high heterogeneity and limitations, the meta-analysis results provide encouraging evidence for the broad-spectrum antiviral property of HBV against numerous viruses, such as influenza viruses, herpes simplex virus, HIV, hepatitis viruses, and emerging coronaviruses. Mechanistically, the HBV components directly disrupt viral replication or do so via body immunomodulation pathways. The main adverse effects of HBV include dose-related cytotoxicity and mild allergic responses, with rare instances (less than 0.1%) of anaphylaxis. Overall, the antiviral roles of HBV are strongly supported in preclinical studies, although the clinical data on humans have limitations. Therefore, improving formulations and conducting safety assessment in future clinical practice, particularly through the use of nanocarriers or combined therapeutic strategies, may enhance the imperative HBV antiviral potency and reduce its limitations.

Background: Chronic hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are among the most important global health issues. Virus-directed CAR-T and CAR-NK are promising strategies capable of targeting virally infected cells. The therapeutic potential, safety, and translational readiness of these platforms have not been fully synthesised. Objectives: This study assessed preclinical and early clinical evidence of CAR-T and CAR-NK immunotherapies against HBV and HIV, including efficacy, safety and translational feasibility. Methods: Databases were searched according to PRISMA 2020 guidelines. For this review, eligible studies included in vitro , in vivo , and clinical studies examining virus-directed CAR lymphocytes. Random-effects models generated pooled standardised mean differences (SMD) and risk ratios (RR). The level of specific evidence was considered by GRADE. Results: Forty-three studies met the inclusion criteria (21 in vitro , 14 in vivo , and 8 clinical). Preclinical HIV CAR-T models demonstrated significant reductions in HIV p24 antigen levels (pooled SMD = −1.15, 95% CI −1.50 to −0.80). Similarly, HBV-directed engineered T-cell studies showed a marked decrease in HBsAg and HBV DNA (SMD = −1.30, 95% CI −1.70 to −0.90). CAR-NK platforms displayed comparable antiviral activity with potentially improved safety profiles. In vivo analyses also indicated consistent suppression of HIV RNA (SMD = −0.92, 95% CI −1.26 to −0.58) and moderate reductions in HBV DNA levels (SMD = −1.05, 95% CI −1.52 to −0.63). In early-phase clinical studies (phase I/II), HIV-directed CAR-T therapies produced modest decreases in circulating HIV RNA (SMD = −0.35, 95% CI −0.60 to −0.12), while HBV-targeted therapies demonstrated small but detectable antiviral responses (SMD = −0.42, 95% CI −0.78 to −0.11). Across clinical cohorts, the incidence of cytokine release syndrome (CRS) remained low, occurring in fewer than 10% of treated patients. Conclusion: Virus-directed CAR-T and CAR-NK therapies show strong preclinical antiviral activity and early clinical signs of activity, showing acceptable safety. Because of heterogeneity, small sample size and limited clinical data, the quality of evidence from this population remains low to moderate. Large and well-controlled trials are necessary to optimise CAR designs, improve persistence, and investigate combinations with latency-reversing or immune-modulating drugs.