Human protein HSF2 helps wake up sleeping cancer-linked viruses, study finds

A newly established team of researchers at Åbo Akademi University, led by Academy Research Fellow Silvia Gramolelli (Faculty of Science and Engineering), has discovered an additional function for Heat Shock Factor 2 (HSF2), a human transcription factor not previously associated with viral processes.

The study, published in PLOS Pathogens, demonstrates the ability of HSF2 to remodel the viral DNA to enable the transition from dormant viral latency to active lytic reactivation. Both human gamma-herpesviruses, specifically Kaposi’s sarcoma herpesvirus (KSHV) and Epstein–Barr virus (EBV), cause several types of cancer.

These viruses establish lifelong persistence in humans and usually remain inactive, or latent, but under certain conditions, they can reactivate and produce new viruses. This reactivation process plays a key role in viral spread and remarkably contributes to cancer development. However, many of the human factors supporting this switch from viral dormancy to activity remain unknown.

The team discovered that HSF2, a transcription factor involved in stress response and development, is a key player in this reactivation process. Notably, HSF2 has never previously been linked to any viral life cycle.

By increasing the levels of HSF2 in virus-infected cells, the researchers observed a boost in viral gene activity. Conversely, reducing HSF2 levels led to a significant drop in viral gene expression. The team also found that HSF2 binds to key viral genes and helps make their chromatin environment more “open,” allowing the virus to activate these genes more easily.

“This research resulted from a collaboration with the Sistonen Research Group, highlighting the importance of synergistic cooperation and open scientific dialog to expand the horizon of scientific findings,” says Lorenza Cutrone, first author of the study and second year Ph.D. student at Åbo Akademi University.

This publication also marks the first scientific contribution from the Viral Oncogenesis research group. The team reports being positively surprised by how quickly the project came together, describing the result as an encouraging and stimulating start to their research journey.

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Abo Akademi University