Maedi infection modulates oncogenic and inflammatory signaling in ovine pulmonary adenomatosis through TLR4/NF-κB and JAK2/STAT3 pathways: A Trojan horse mechanism.

Abstract

Ovine pulmonary adenomatosis (OPA) is a contagious pulmonary tumor of sheep caused by Jaagsiekte sheep retrovirus, whereas Maedi is a chronic lentiviral infection characterized by persistent pulmonary inflammation. Although both diseases affect the lung, their interaction during natural co-infection remains poorly understood. This study investigated how chronic Maedi infection may influence inflammatory, oncogenic, and apoptotic signaling pathways in OPA-affected lung tissue. Lung samples from naturally infected sheep were classified by PCR and histopathological examination into Maedi (n&#x202f;=&#x202f;6), OPA (n&#x202f;=&#x202f;6), and Maedi+OPA co-infection (n&#x202f;=&#x202f;6) groups. Key inflammatory, oncogenic, and apoptotic markers were evaluated at the protein and transcript levels. Maedi and mixed infection groups showed increased activation of the TLR4/NF-&#x3ba;B pathway and elevated pro-inflammatory cytokine expression compared with OPA alone. These changes were associated with significant alterations in apoptotic markers, including increased Bax and Caspase-3 expression and decreased Bcl-2 levels (p&#x202f;<&#x202f;0.05). In contrast, OPA samples exhibited higher activity of JAK2/STAT3 and PI3K/AKT/mTOR signaling pathways, which appeared reduced under Maedi-associated conditions. Overall, these findings suggest that chronic Maedi infection may modulate the pulmonary microenvironment by influencing inflammatory, apoptotic, and oncogenic signaling pathways in OPA. This immunomodulatory interaction may be relevant for understanding host-virus dynamics in naturally occurring virus-induced lung tumors.