Interferon regulatory factor 5.2 acts as a transcription repressor of Epidermodysplasia verruciformis-associated human papillomaviruses

Abstract

Human papillomavirus type 8 (HPV8) poses a high risk for malignant conversion of skin lesions in patients with Epidermodysplasia verruciformis (Ev). Its oncogene promoter P(175) contains the conserved sequence motifs CCAAC, M29, and an A/T-rich region, which are common in many Ev-associated viruses. In human keratinocytes P(175) shows very weak activity. We used the M29 sequence as bait in a yeast-one-hybrid screen of a HaCaT cDNA library to identify interacting proteins regulating P(175). We report the identification of a cDNA encoding the interferon regulatory factor IRF5.2. In band shift assays the physical interaction of IRF5.2 and M29 was confirmed, and also its binding to the negative regulatory element (NRE) of HPV8 could be demonstrated. In transient reporter gene assays, overexpressed IRF5.2 acts as a transcriptional repressor of HPV8 and the Ev-associated HPV types 5, 14, and 25. These results indicate that the cellular transcription factor IRF5.2 is a general transcription repressor of Ev-associated HPV.