SI: Silencing is overcome by positioning transgene next to viral or cellular insulators at the LAT or ICP4 loci. #ccvi24

SI: Deletion of all immediate early genes eliminates cytotoxicity and leads to transgene payload silencing. #ccvi24

Now: Selene Ingusci: Comparison of viral and cellular insulators in promoting durable HSV-1 vector mediated transgene expression in muscle and brain. #ccvi24 🧪🧬🔄🖥️

TT: Inverted repeats have a role in accumulation and maintenance of transduced viral genomes in quiescent infection of normal cells. Do inverted repeats play same role during latent infection? #ccvi24

TT: KTT3 viral DNA levels higher and tend to be associated with more euchromatin than JDNI7 in normal human foreskin fibroblast cells #ccvi24

TT: KTT3 express higher levels of GFP in human sensory neurons 21 days post infection #ccvi24

TT: Role of inverted repeat genomic structure elements, such as internal a' sequence, CTCF-binding sites → structural changes in viral DNA template. #ccvi24

TT: Inverted repeat sequences in KTT3 increase viral growth in complementing cells, late gene expression during lytic infection in complementing cells. #ccvi24

TT: ICP0 retained: high level of transgene expression (anti-silencing effects of ICP0). Transient due to residual cytotoxicity. ICP0 deleted: low level transgene expression (likely epigenetic silencing), reduced cytotoxicity #ccvi24

TT: Deleting immediate early genes in HSV-1 vectors. Deletion of ICP4/27/22/47 prevents lytic replication, reduces cytotoxicity. #ccvi24

Now: Thao Tran: Internal inverted repeats in a new HSV-1 gene therapy vector improve replication and transduction #ccvi24 🧪🧬🔄🖥️

Now: Ben Gewurz: Chromatin control of the Epstein-Barr Virus B-cell lytic switch #ccvi24 🧪🧬🔄🖥️

Human papillomavirus integration transforms chromatin to drive oncogenesis - Genome Biology Background Human papillomavirus (HPV) drives almost all cervical cancers and up to 70% of head and neck cancers. Frequent integration into the host genome occurs predominantly in tumorigenic types of ...

Anyway, here's our paper, it's really good, check it out #ccvi24 🧪🧬🔄🖥️ genomebiology.biomedcentral.com/articles/10....

Now: Michael Hoffman: Human papillomavirus integration transforms chromatin to drive oncogenesis #ccvi24 🧪🧬🔄🖥️

DM: EBNA-LP and EBNA2 co-localize with YY1 in lymphoblastoid cell lines on promoters essential for B cell immortalization. Upon EBV infection, H3K27ac increases at YY1/EBNA-LP co-bound regions; H3K4me1 decreases #ccvi24

DM briefly shows some RNA-seq differential expression results. Concerned that so many of the outliers are Ig-related or non-coding RNAs. #ccvi24

DM: EBNA-LP knockout causes change in chromatin accessibility and gene expression. 1790 differential ATAC-seq peaks #ccvi24

DM: YY1 binding decreases upon EBV infection. H3K4me1 decreases in these regions in ENCODE lymphoblastoid cell lines. YY1/EBNA-LP mediated loops more frequent after transformation of B cells. #ccvi24

DM: YY1 and EBNA-LP/EBNA2 co-localize at YY1 HiChIP anchors. YY1 and EBNA2/LP form different loop types (enhancer-enhancer vs. enhancer-promoter vs. promoter-promoter). #ccvi24

DM: YY1 colocalizes with EBNA-LP and EBNA2 #ccvi24

DM: What could cause rearrangement in YY1 binding? EBNA-LP interactws with YY1 at its binding sites. #ccvi24

DM: IPA enrichment of YY1 regulation of B cell-specific pathways. #ccvi24

DM: YY1 ChIP reveals differences between latency types. Mostly binds at promoters in proliferative latency. #ccvi24

DM: Yin-yang-1 (YYI) named because can be coactivator or corepressor, works with CTCF to organize genome architecture #ccvi24

DM: EBV infection determines rearrangement in genome architecture. 1/Primary infection of B cell. 2/Reorganization of genome architecture. #ccvi24

Now: Davide Maestri: EBNA-LP cooperates with YY1 and CTCF architectural proteins in reshaping B cell genome #ccvi24 🧪🧬🔄🖥️

Q on cause and effect. LK: Expressing HCMV viral transcriptional regulators and investigating. Read the paper when it comes out #ccvi24

LK: Q: Why Hippo? LK: Named because mutations in Drosophila make larva look like hippopotamuses. #ccvi24

LK: Many viruses target places specific to individual host transcription factors #ccvi24

LK: HCMV infection targets TEAD1-induced Hippo signaling through four distinct mechanisms #ccvi24