Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence

Qiming Sun, Toshiki Tsurimoto, Franceline Juillard, Lin Li, Shijun Li, Erika De León Vázquez, She Chen, Kenneth Kaye

研究成果: ジャーナルへの寄稿記事

29 引用 (Scopus)

抄録

Kaposi's sarcoma-associated herpesvirus (KSHV) latently infects tumor cells and persists as a multiple-copy, extrachromosomal, circular episome. To persist, the viral genome must replicate with each cell cycle. The KSHV latency-associated nuclear antigen (LANA) mediates viral DNA replication and persistence, but little is known regarding the underlying mechanisms. We find that LANA recruits replication factor C (RFC), the DNA polymerase clamp [proliferating cell nuclear antigen (PCNA)] loader, to drive DNA replication efficiently. Mutated LANA lacking RFC interaction was deficient for LANA-mediated DNA replication and episome persistence. RFC depletion had a negative impact on LANA's ability to replicate and maintain viral DNA in cells containing artificial KSHV episomes or in infected cells, leading to loss of virus. LANA substantially increased PCNA loading onto DNA in vitro and recruited RFC and PCNA to KSHV DNA in cells. These findings suggest that PCNA loading is a rate-limiting step in DNA replication that is incompatible with viral survival. LANA enhancement of PCNA loading permits efficient virus replication and persistence, revealing a previously unidentified mechanism for KSHV latency.

元の言語英語
ページ(範囲)11816-11821
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
111
発行部数32
DOI
出版物ステータス出版済み - 8 12 2014

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Human Herpesvirus 8
DNA-Directed DNA Polymerase
Virus Replication
Replication Protein C
Proliferating Cell Nuclear Antigen
DNA Replication
Plasmids
Viral DNA
Artificial Cells
Viral Genome
DNA
latency-associated nuclear antigen
Cell Cycle
Viruses
Neoplasms

All Science Journal Classification (ASJC) codes

  • General

これを引用

Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence. / Sun, Qiming; Tsurimoto, Toshiki; Juillard, Franceline; Li, Lin; Li, Shijun; De León Vázquez, Erika; Chen, She; Kaye, Kenneth.

:: Proceedings of the National Academy of Sciences of the United States of America, 巻 111, 番号 32, 12.08.2014, p. 11816-11821.

研究成果: ジャーナルへの寄稿記事

Sun, Qiming ; Tsurimoto, Toshiki ; Juillard, Franceline ; Li, Lin ; Li, Shijun ; De León Vázquez, Erika ; Chen, She ; Kaye, Kenneth. / Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence. :: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; 巻 111, 番号 32. pp. 11816-11821.
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abstract = "Kaposi's sarcoma-associated herpesvirus (KSHV) latently infects tumor cells and persists as a multiple-copy, extrachromosomal, circular episome. To persist, the viral genome must replicate with each cell cycle. The KSHV latency-associated nuclear antigen (LANA) mediates viral DNA replication and persistence, but little is known regarding the underlying mechanisms. We find that LANA recruits replication factor C (RFC), the DNA polymerase clamp [proliferating cell nuclear antigen (PCNA)] loader, to drive DNA replication efficiently. Mutated LANA lacking RFC interaction was deficient for LANA-mediated DNA replication and episome persistence. RFC depletion had a negative impact on LANA's ability to replicate and maintain viral DNA in cells containing artificial KSHV episomes or in infected cells, leading to loss of virus. LANA substantially increased PCNA loading onto DNA in vitro and recruited RFC and PCNA to KSHV DNA in cells. These findings suggest that PCNA loading is a rate-limiting step in DNA replication that is incompatible with viral survival. LANA enhancement of PCNA loading permits efficient virus replication and persistence, revealing a previously unidentified mechanism for KSHV latency.",
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AU - De León Vázquez, Erika

AU - Chen, She

AU - Kaye, Kenneth

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