Using a primary human NPC culture system and a SCID HIV-1 encephalitis (HIVE) mouse model, we demonstrate that the STAT3 pathway is crucial for HIV-1-infected and immune-activated MDM-induced NPC astrogliogenesis and provide evidence that this effect is at least partially mediated by the action of TNF-α. Here, STAT3 is linked to nasopharyngeal carcinoma.