Association of HHV-6 Reactivation with NLRP3 Inflammasome Activation in Chemotherapy-Treated Iraqi Cancer Patients: A Cross-Sectional Study

Human herpesvirus 6 (HHV-6) typically remains latent but can reactivate during immunosuppression caused by chemotherapy, potentially driving immune dysregulation. The NLRP3 inflammasome is a critical innate immune complex mediating pro-inflammatory signaling implicated in tumor progression and treatment toxicity. This study investigated the association between HHV-6 antigenemia and NLRP3 inflammasome activation in 193 chemotherapy-treated cancer patients at the Oncology Hospital in Al-Najaf, Iraq. Serological markers for HHV-6 IgG, IgM, and circulating viral antigen, along with serum NLRP3 levels, were quantified using ELISA. Active HHV-6 antigenemia was observed in over half the cohort, with 56.5% positive for IgM and 42.5% exhibiting antigenemia. Elevated serum NLRP3 levels were detected in 65.8% of patients and correlated significantly with HHV-6 antigen presence, particularly in hematological and genitourinary cancers. Viral antigenemia and inflammasome activity were more prominent in females and older patients. Host gene analysis revealed Hepcidin (HAMP) polymorphisms and altered expression compared to healthy controls, suggesting links between iron metabolism, viral antigenemia, and inflammasome activity. These findings highlight a potential mechanistic connection between HHV-6 antigenemia and inflammasome-driven inflammation, which may contribute to chemotherapy-associated immune dysregulation. Monitoring HHV-6 antigenemia and NLRP3 activation may offer valuable insight into the inflammatory status of cancer patients undergoing chemotherapy.