KSHV episome tethering sites on host chromosomes and regulation of latency-lytic switch by CHD4
Copyright policy )KSHV episome tethering sites on host chromosomes and regulation of latency-lytic switch by CHD4
Kaposi sarcoma-associated herpesvirus (KSHV) establishes a latent infection in the cell nucleus, but where KSHV episomal genomes are tethered and the mechanisms underlying KSHV lytic reactivation are unclear. Here, we study the nuclear microenvironment of KSHV episomes and show that the KSHV latency-lytic replication switch is regulated via viral long non-coding (lnc)RNA-CHD4 (chromodomain helicase DNA binding protein 4) interaction. KSHV episomes localize with CHD4 and ADNP proteins, components of the cellular ChAHP complex. The CHD4 and ADNP proteins occupy the 5'-region of the highly inducible lncRNAs and terminal repeats of the KSHV genome together with latency-associated nuclear antigen (LANA). Viral lncRNA binding competes with CHD4 DNA binding, and KSHV reactivation sequesters CHD4 from the KSHV genome, which is also accompanied by detachment of KSHV episomes from host chromosome docking sites. We propose a model in which robust KSHV lncRNA expression determines the latency-lytic decision by regulating LANA/CHD4 binding to KSHV episomes.
- National Cancer Institute United States
- University of California, Davis United States
- UNIVERSITY OF CALIFORNIA AT DAVIS
- University of California, San Francisco United States
- UNIVERSITY OF CALIFORNIA DAVIS
Medical Physiology, ChAHP complex, DNA virus, Tumor Microenvironment, 2.1 Biological and endogenous factors, Viral, Antigens, Viral, ADNP, Cancer, CP: Microbiology, Sarcoma, Biological Sciences, Virus Latency, Biological sciences, Infectious Diseases, mini-TurboID, Herpesvirus 8, Human, HIV/AIDS, Long Noncoding, RNA, Long Noncoding, Infection, Human, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Plasmids, 570, LANA, Bioinformatics and Computational Biology, lncRNAs, viral reactivation, 610, Kaposi, KSHV, Article, Chromosomes, Genetics, Humans, Antigens, Herpesvirus 8, Sarcoma, Kaposi, Human Genome, CHD4, episome tethering, Emerging Infectious Diseases, Sexually Transmitted Infections, RNA, Biochemistry and Cell Biology
Medical Physiology, ChAHP complex, DNA virus, Tumor Microenvironment, 2.1 Biological and endogenous factors, Viral, Antigens, Viral, ADNP, Cancer, CP: Microbiology, Sarcoma, Biological Sciences, Virus Latency, Biological sciences, Infectious Diseases, mini-TurboID, Herpesvirus 8, Human, HIV/AIDS, Long Noncoding, RNA, Long Noncoding, Infection, Human, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Plasmids, 570, LANA, Bioinformatics and Computational Biology, lncRNAs, viral reactivation, 610, Kaposi, KSHV, Article, Chromosomes, Genetics, Humans, Antigens, Herpesvirus 8, Sarcoma, Kaposi, Human Genome, CHD4, episome tethering, Emerging Infectious Diseases, Sexually Transmitted Infections, RNA, Biochemistry and Cell Biology
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