Human Protein HSF2 Activates Dormant Cancer-Associated Viruses, New Research Shows

A groundbreaking study by researchers at Åbo Akademi University has revealed a novel function of the human transcription factor HSF2, previously not associated with viral activity. Published in PLOS Pathogens, the research uncovers how HSF2 plays a crucial role in reactivating latent gamma-herpesviruses, such as Kaposi's sarcoma herpesvirus (KSHV) and Epstein–Barr virus (EBV), which are linked to various cancers.

These viruses establish lifelong latency in human cells, remaining dormant until specific signals trigger their reactivation. Reactivation involves switching from a latent state to active viral replication, which can lead to the proliferation of new viruses and contribute significantly to cancer development. However, the human factors influencing this switch have largely remained a mystery.

The research team discovered that HSF2, known for its involvement in stress response and development, directly influences viral gene expression. Increasing HSF2 levels in infected cells resulted in heightened viral activity, while decreasing its levels suppressed viral gene expression. The mechanism involves HSF2 binding to essential viral genes and remodeling the local chromatin environment to an open state, thereby facilitating viral gene activation.

This discovery highlights a surprising and critical role of HSF2, expanding our understanding of the cellular processes that enable viruses to exit dormancy. It also suggests new potential targets for therapeutic interventions aimed at controlling virus-linked cancers.

The study exemplifies successful collaboration, particularly with the Sistonen Research Group, emphasizing how open scientific dialogue fosters new insights. It also marks the first contribution from the Viral Oncogenesis research group at Åbo Akademi University, inspiring further research into the complex interactions between human proteins and viruses.

This research not only advances our knowledge of viral reactivation mechanisms but also opens new avenues for cancer prevention and treatment strategies related to virus-induced oncogenesis.