The Intrinsic Antiviral Defense to Incoming HSV-1 Genomes Includes Specific DNA Repair Proteins and Is Counteracted by the Viral Protein ICP0
Figure 7
H2AX is beneficial for HSV-1 replication while RNF8 represses viral genomes.
(A) H2AX-/- MEFs or matched controls were infected with wild-type or ICP0-null virus. Relative probabilities of plaque formation were calculated by counting the numbers of plaques on the different cell lines at each separate dilution of virus. Infections were carried out at least in duplicate and the experiment was repeated four times. Data are represented as mean +/- SEM. (B) RNF8-/- MEFs expressing RNF8 or empty vector were infected with WT or ICP0-null virus at an MOI of 0.01. ICP27 transcripts were detected at 2 or 5 hpi and normalized to a cellular control. Data were analyzed by comparing transcription in the presence of RNF8 to transcription in the absence of RNF8 and therefore represent fold repression by RNF8 for each virus. Experiments were performed in duplicate and averaged. Results are representative of three independent experiments and the error is one standard deviation of the duplicate samples. (C) Model showing the parallels between sites of cellular DNA damage and sites associated with incoming HSV-1 genomes and the role of central role of ICP0, RNF8 and RNF168 in disrupting both structures.
