Scientists have discovered that the herpes simplex virus type 1 (HSV-1) reorganizes the human genome to access genes that help it replicate. This finding offers new insights into how viruses manipulate their hosts, potentially leading to better treatments.
Researchers at the Centre for Genomic Regulation (CRG) in Barcelona found that HSV-1 reshapes the three-dimensional structure of the human genome. This allows the virus to access the host's genes, which it needs to multiply. The study, published in Nature Communications, reveals a previously unknown mechanism of viral manipulation.
The study showed that blocking a single human enzyme, topoisomerase I, completely stops HSV-1 from reorganizing the human genome during infection, thus halting viral replication. In cell cultures, inhibiting this enzyme prevented infection before the virus could produce new particles. This discovery suggests a novel strategy to control a virus that infects nearly four billion people worldwide.
The team used super-resolution microscopy, which can visualize structures as small as 20 nanometers, and Hi-C, a technique that reveals which DNA fragments are interacting within the nucleus. They combined these techniques to understand how HSV-1 hijacks human cells. They found that the virus hijacks the human RNA polymerase II enzyme to help synthesize its own proteins.
The virus's actions cause transcription to shut down across the host genome, leading to the chromatin – the natural state of human DNA within cells – compacting into a dense shell. This was unexpected, as it was previously thought that chromatin structure dictated transcription. This research suggests a two-way relationship between activity and structure.
HSV-1 affects two out of every three people under 50. While most infections are asymptomatic or cause recurring cold sores, the virus can rarely lead to blindness or life-threatening illness. This research could help address the global health challenge posed by HSV-1, which is prevalent and can cause recurrent outbreaks. Although treatments exist to manage symptoms, drug-resistant strains are emerging, and there is no cure.