2024-03-28T22:27:58Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1150282018-12-12T12:13:58Zcom_10261_79com_10261_1col_10261_332
DIGITAL.CSIC
author
Jäger, Wiebke
author
Santag, Susann
author
Weidner-Glunde, Magdalena
author
Gellermann, Eva
author
Kati, Semra
author
Pietrek, Marcel
author
Viejo-Borbolla, Abel
author
Schulz, Thomas F.
funder
European Commission
funder
German Research Foundation
2015-05-12T10:27:14Z
2015-05-12T10:27:14Z
2012
Journal of Virology 86 (12): 6745- 6757 (2012)
http://hdl.handle.net/10261/115028
10.1128/JVI.06840-11
http://dx.doi.org/10.13039/501100000780http://dx.doi.org/10.13039/501100001659
22514345
Kaposi's sarcoma herpesvirus (KSHV) belongs to the gamma-2 Herpesviridae and is associated with three neoplastic disorders: Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). The viral latency-associated nuclear antigen 1 (LANA) is expressed in all latently KSHV-infected cells and is involved in viral latent replication and maintenance of the viral genome. We show that LANA interacts with the ubiquitin-specific protease USP7 through its N-terminal TRAF (tumor necrosis factor [TNF] receptor-associated factor) domain. This interaction involves a short sequence (amino acids [aa] 971 to 986) within the C-terminal domain of LANA with strong similarities to the USP7 binding site of the Epstein-Barr virus (EBV) EBNA-1 protein. A LANA mutant with a deletion of the identified USP7 binding site showed an enhanced ability to replicate a plasmid containing the KSHV latent origin of replication but was comparable to the wild-type LANA (LANA WT) with regard to the regulation of viral and cellular promoters. Furthermore, the LANA homologues of two other gamma-2 herpesviruses, MHV68 and RRV, also recruit USP7. Our findings suggest that recruitment of USP7 to LANA could play a role in the regulation of viral latent replication. The recruitment of USP7, and its role in herpesvirus latent replication, previously described for the latent EBNA-1 protein of the gamma-1 herpesvirus (lymphocryptovirus) EBV (M. N. Holowaty et al., J. Biol. Chem. 278:29987-29994, 2003), may thereby be a conserved feature among gammaherpesvirus latent origin binding proteins.
eng
openAccess
The ubiquitin-specific protease USP7 Modulates the replication of kaposi's sarcoma-associated herpesvirus latent episomal DNA
artículo
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Abel_Viejo_Borbolla_The_Ubitiquin.pdf.txt
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Abel_Viejo_Borbolla_The_Ubitiquin.pdf.txt