Extended Data Fig. 2: (Related to Fig. 2). Analysis of host cell Z-RNAs and ZBP1-bound RNAs.

a, Overview of peak calling and identification of unique dsRNA clusters. Arrows extending from the RIP track indicate the processing stages at which the RIP signal is utilized. Dashed boxes highlight dsRNA clusters which include one or more putative dsRNAs (e.g., the central and rightmost clusters, based on reverse-complementary sequences) and/or unresolved - but highly reproducible - RIP enrichment sites lacking a clear complementary pair (e.g., the leftmost cluster). b, Overview of the dsRNA analyses. Virus-induced host cell Z-forming dsRNAs were defined as those showing RIP enrichment in the target RIP (Z22 or FLAG) and increased levels in infected cells, either in total RNA or Z22 RIP reads, compared to mock-treated controls. These are summarized in a Rx2 table where R is the number of unique RIP-enriched Z-RNAs which are significantly overexpressed in infected cells after exclusion of the K dsRNAs unaffected by the infection. c, Global overlap of virus-induced host cell Z-RNAs (Z22-enriched) and ZBP1-bound (anti-FLAG enriched) RNAs from FLAG-ZBP1 MEFs infected with WT HSV-1 (MOI = 2, 8 h post-infection). Hypergeometric p-value, indicative of the odds that the overlap between the two pulldowns arises from chance alone, is shown above the Venn diagram. d, Genomic distribution of virus-induced host cell Z-RNAs enriched in FLAG RIP-seq from FLAG-ZBP1 MEFs infected with WT HSV-1 (MOI = 2, 8 h post-infection). e, Source of inverted reverse complement sequences within virus-induced host cell Z-RNAs enriched in FLAG RIP-seq from FLAG-ZBP1 MEFs infected with WT HSV-1 (MOI = 2, 8 h post-infection). The ‘Unresolved’ category includes Z-forming RNAs whose secondary structures could not be readily solved. f, Detailed distribution of inverted EREs in virus-induced host cell Z-RNAs enriched in FLAG RIP-seq from FLAG-ZBP1 MEFs infected with WT HSV-1 (MOI = 2, 8 h post-infection).