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  • PML-NB-dependent type I interferon memory results in a restricted form of HSV latency.

PML-NB-dependent type I interferon memory results in a restricted form of HSV latency.

EMBO reports (2021-07-02)
Jon B Suzich, Sean R Cuddy, Hiam Baidas, Sara Dochnal, Eugene Ke, Austin R Schinlever, Aleksandra Babnis, Chris Boutell, Anna R Cliffe
ABSTRACT

Herpes simplex virus (HSV) establishes latent infection in long-lived neurons. During initial infection, neurons are exposed to multiple inflammatory cytokines but the effects of immune signaling on the nature of HSV latency are unknown. We show that initial infection of primary murine neurons in the presence of type I interferon (IFN) results in a form of latency that is restricted for reactivation. We also find that the subnuclear condensates, promyelocytic leukemia nuclear bodies (PML-NBs), are absent from primary sympathetic and sensory neurons but form with type I IFN treatment and persist even when IFN signaling resolves. HSV-1 genomes colocalize with PML-NBs throughout a latent infection of neurons only when type I IFN is present during initial infection. Depletion of PML prior to or following infection does not impact the establishment latency; however, it does rescue the ability of HSV to reactivate from IFN-treated neurons. This study demonstrates that viral genomes possess a memory of the IFN response during de novo infection, which results in differential subnuclear positioning and ultimately restricts the ability of genomes to reactivate.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Interferon-β Protein, Recombinant mouse, Interferon-β Protein, Recombinant mouse.
Sigma-Aldrich
Interferon-γ Protein, Recombinant mouse, The Interferon-gamma protein (or IFN-gamma protein) is a regulatory protein produced by activated NK cells & CD4+TCRalpha/beta+, CD8+TCRalpha/beta+ & TCRgamma/delta+ T cells.
Sigma-Aldrich
Interferon-α A Protein, Recombinant mouse, Interferon-α A Protein, Recombinant mouse.