Abstract
BACKGROUND: Mpox disease, caused by the monkeypox virus (MPXV), remains a global health concern with nearly half of all cases occurring among individuals with human immunodeficiency virus (HIV). While recent studies have advanced our understanding of poxvirus pathogenesis, the molecular effects of mpox and HIV coinfection are still poorly understood. This study uses dual RNA sequencing (RNA-seq) to characterize host and viral gene expression in skin lesion swabs from people with mpox, including individuals with and without HIV. METHODS: Our cohort included 19 participants with confirmed MPXV infection, with 53 total skin lesion swabs collected during the early (7-13 days post-symptom onset) and late (15-21 days post-symptom onset) stages of mpox disease. RNA-seq was used to assess both host and MPXV gene expression over time in participants with and without HIV. RESULTS: HIV-positive participants showed upregulation of MPXV genes involved in immune evasion and viral replication. Conversely, host immune pathways, such as interferon signaling, apoptosis, and chemokine recruitment, were downregulated in participants with HIV. Pathway enrichment analysis revealed dysregulated immune signaling and autophagy, key processes for viral clearance. These findings suggest that HIV-related immunosuppression may enhance MPXV replication and prolong disease. CONCLUSIONS: This study highlights the use of dual RNA-seq in uncovering molecular interactions between host and virus during mpox infections. Our findings offer insights into how HIV coinfection may alter MPXV pathogenesis, with implications for treatment strategies and disease management in immunocompromised populations.