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HSV-1 Genome Subnuclear Positioning and Associations with Host-Cell PML-NBs and Centromeres Regulate LAT Locus Transcription during Latency in Neurons

Figure 4

PML-NBs form around HSV-1 genomes in neurons.

(A) Co-localization of HSV-1 genomes with PML protein. TG sections from mock-infected and latently infected (SC16/lip) mice (28 d.p.i.) were stained by immuno-FISH to co-detect the HSV-1 genome and PML protein. The boxed areas show single-channel images. Scale bar = 5 µm. (B) The HSV-1 genome associates with major PML-NB components. TG sections from latently infected mice were stained by immuno-DNA-FISH using anti-ATRX or anti-Daxx antibody and HSV-1 probe. HSV-1 genomes associated with ATRX or Daxx are indicated by arrows and enlarged in the insets. (C) TG sections from the same mouse as in (B) were stained by dual immuno-FISH using anti-PML and anti-Daxx antibodies and HSV-1 probe. The arrow shows an HSV-1-containing PML-NB stained with anti-Daxx antibody. (D) Confocal microscopic analysis of an HSV-1-containing PML-NB, showing (by fluorescence line-scan measurement and 3D reconstruction of a confocal Z-stack) that the HSV-1 DNA-FISH signal is localized within the PML-NB.

Figure 4

doi: https://doi.org/10.1371/journal.ppat.1002852.g004