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Activating and repressive FOX family proteins regulate HSV-1 chromatin and the lytic-latent balance through epigenetic modulators

GSE299792 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2026/01/09 Platform GPL30173
Summary
Herpes simplex virus 1 (HSV-1) switches between lytic and latent infections in neurons, yet the switch mechanisms remain obscure. Here we identify forkhead box (FOX) family proteins that can strongly activate or repress HSV-1 replication particularly in neuronal cells. Expression of activating FOX genes (Foxa, Foxc, Foxe, Foxf) is ordinarily low and expression of repressive FOX genes (Foxk) is high in neurons. Lytic HSV-1 infection and other stresses can increase activating FOX gene expression. Such overexpression or knockout of endogenous FOXK1 promotes reactivation from latency. These FOX proteins broadly associate with the viral genome and regulate viral gene transcription through epigenetic modulators. FOXF1 associates with histone acetyltransferases CBP and P300 to open viral chromatin. FOXK1 collaborates with SIN3A, a known cofactor of histone deacetylation, and MAX to suppress HSV-1 replication and antagonize activating FOX proteins. Thus, HSV-1 uses FOX family members with opposing effects to regulate the lytic-latent balance.
Published in
Counteracting FOX proteins epigenetically control the herpesvirus lytic-latent balance
Xiang Y, Yang X, Zhang J et al. · Nature communications 2026 · PMID 41629328 · doi:10.1038/s41467-026-68915-1
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Also filed as BioProject PRJNA1276530 and SRA study SRP591922. Searching any of these in the dataset finder brings you back here.

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