biostudies-literatureUnknownDella Fera ANThe circular, double-stranded DNA genomes of Human papillomaviruses (HPV) exist in a nucleosomal state throughout the infectious cycle and rely on host histone epigenetic modifications and chromatin assembly processes to promote various phases of the viral life cycle. Here, we show that the histone H3.3 chaperone HIRA and its associated complex members are recruited to HPV replication factories during the late phase of the HPV life cycle. HIRA is also recruited to HPV replication factories generated by amplification of a replicon with a minimal origin and expression of the viral replication proteins E1 and E2, demonstrating that the E1 and E2 proteins are sufficient for HIRA recruitment. Downregulation of HIRA expression reduces HPV31 DNA amplification and viral transcription in differentibioRxiv : the preprint server for biology2025.09.05.674520https://www.ebi.ac.uk/biostudies/studies/S-EPMC12466780biostudies-literatureChromatin assembly by the histone chaperone HIRA facilitates Human Papillomavirus replication.PMC12466780Della Fera ANMcBride AAChen DfalseChromatin assembly by the histone chaperone HIRA facilitates Human Papillomavirus replication.The circular, double-stranded DNA genomes of Human papillomaviruses (HPV) exist in a nucleosomal state throughout the infectious cycle and rely on host histone epigenetic modifications and chromatin assembly processes to promote various phases of the viral life cycle. Here, we show that the histone H3.3 chaperone HIRA and its associated complex members are recruited to HPV replication factories during the late phase of the HPV life cycle. HIRA is also recruited to HPV replication factories generated by amplification of a replicon with a minimal origin and expression of the viral replication proteins E1 and E2, demonstrating that the E1 and E2 proteins are sufficient for HIRA recruitment. Downregulation of HIRA expression reduces HPV31 DNA amplification and viral transcription in differenti2025-01-01T00:00:00Z2025 Sep2026-05-20T03:21:57.772Z2026-05-20T03:14:33.586ZS-EPMC124667804101963510.1101/2025.09.05.674520