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Phase separation and DAXX redistribution contribute to LANA nuclear body and KSHV genome dynamics during latency and reactivation.
Vladimirova, Olga; De Leo, Alessandra; Deng, Zhong; Wiedmer, Andreas; Hayden, James; Lieberman, Paul M.
Affiliation
  • Vladimirova O; The Wistar Institute, Philadelphia, United States of America.
  • De Leo A; Department of Immunology, H. Lee Moffit Cancer and Research Center, Tampa Florida, United States of America.
  • Deng Z; The Wistar Institute, Philadelphia, United States of America.
  • Wiedmer A; The Wistar Institute, Philadelphia, United States of America.
  • Hayden J; The Wistar Institute, Philadelphia, United States of America.
  • Lieberman PM; The Wistar Institute, Philadelphia, United States of America.
PLoS Pathog ; 17(1): e1009231, 2021 01.
Article in En | MEDLINE | ID: mdl-33471863
Liquid-liquid phase separation (LLPS) can drive formation of diverse and essential macromolecular structures, including those specified by viruses. Kaposi's Sarcoma-Associated Herpesvirus (KSHV) genomes associate with the viral encoded Latency-Associated Nuclear Antigen (LANA) to form stable nuclear bodies (NBs) during latent infection. Here, we show that LANA-NB formation and KSHV genome conformation involves LLPS. Using LLPS disrupting solvents, we show that LANA-NBs are partially disrupted, while DAXX and PML foci are highly resistant. LLPS disruption altered the LANA-dependent KSHV chromosome conformation but did not stimulate lytic reactivation. We found that LANA-NBs undergo major morphological transformation during KSHV lytic reactivation to form LANA-associated replication compartments encompassing KSHV DNA. DAXX colocalizes with the LANA-NBs during latency but is evicted from the LANA-associated lytic replication compartments. These findings indicate the LANA-NBs are dynamic super-molecular nuclear structures that partly depend on LLPS and undergo morphological transitions corresponding to the different modes of viral replication.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sarcoma, Kaposi / Nuclear Proteins / Genome, Viral / Molecular Chaperones / Herpesvirus 8, Human / Intranuclear Inclusion Bodies / Co-Repressor Proteins / Antigens, Viral Limits: Humans Language: En Journal: PLoS Pathog Year: 2021 Document type: Article Affiliation country: United States Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sarcoma, Kaposi / Nuclear Proteins / Genome, Viral / Molecular Chaperones / Herpesvirus 8, Human / Intranuclear Inclusion Bodies / Co-Repressor Proteins / Antigens, Viral Limits: Humans Language: En Journal: PLoS Pathog Year: 2021 Document type: Article Affiliation country: United States Country of publication: United States