The Minimal Replicator Element of the Kaposi's Sarcoma-associated Herpesvirus Terminal Repeat Supports Replication in a Semiconservative and Cell-cycle-dependent Manner

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2006 Dec 8

PMID 17151118

Citations 26

Authors

Subhash C Verma

Tathagata Choudhuri

Erle S Robertson

Affiliations

Soon will be listed here.

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) persists as episomes in infected cells by circularizing at the terminal repeats (TRs). The KSHV episome carries multiple reiterated copies of the terminal repeat, and each copy is capable of supporting replication. Expression of the latency-associated nuclear antigen (LANA) is critical for the replication of TR-containing plasmids. A 32-bp sequence upstream of LANA binding site 1 (LBS1), referred to as RE (replication element), along with LANA binding sites 1 and 2 (RE-LBS1/2), is sufficient to support replication (J. Hu and R. Renne, J. Virol. 79:2637-2642, 2005). In this report we demonstrate that the minimal replicator element (RE-LBS1/2) replicates in synchrony with the host cellular DNA, and only once, in a cell-cycle-dependent manner. Overexpression of the mammalian replication inhibitor geminin blocked replication of the plasmid containing the minimal replicator element, confirming the involvement of the host cellular replication control mechanism, and prevented rereplication of the plasmid in the same cell cycle. Overexpression of Cdt1 also rescued the replicative ability of the RE-LBS1/2-containing plasmids. A chromatin immunoprecipitation assay performed using anti-origin recognition complex 2 (alpha-ORC2) and alpha-LANA antibodies from cells transfected with RE-LBS1/2, RE-LBS1, LBS1, or RE showed the association of ORC2 with the RE region. Expression of LANA increased the number of copies of chromatin-bound DNA of replication elements, suggesting that LANA is important for the recruitment of ORCs and may contribute to the stabilization of the replication protein complexes at the RE site.

Citing Articles

Unraveling the Kaposi Sarcoma-Associated Herpesvirus (KSHV) Lifecycle: An Overview of Latency, Lytic Replication, and KSHV-Associated Diseases.

Losay V, Damania B Viruses. 2025; 17(2).

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Latently KSHV-Infected Cells Promote Further Establishment of Latency upon Superinfection with KSHV.

Gam Ze Letova C, Kalt I, Shamay M, Sarid R Int J Mol Sci. 2021; 22(21).

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Herpesviral Latency-Common Themes.

Weidner-Glunde M, Kruminis-Kaszkiel E, Savanagouder M Pathogens. 2020; 9(2).

PMID: 32075270 PMC: 7167855. DOI: 10.3390/pathogens9020125.

KSHV-encoded LANA protects the cellular replication machinery from hypoxia induced degradation.

Singh R, Lamplugh Z, Lang F, Yuan Y, Lieberman P, You J PLoS Pathog. 2019; 15(9):e1008025.

PMID: 31479497 PMC: 6743784. DOI: 10.1371/journal.ppat.1008025.

Towards Better Understanding of KSHV Life Cycle: from Transcription and Posttranscriptional Regulations to Pathogenesis.

Yan L, Majerciak V, Zheng Z, Lan K Virol Sin. 2019; 34(2):135-161.

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