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Title: ORF73 LANA homologs of RRV and MneRV2 contain an extended RGG/RG-rich nuclear and nucleolar localization signal that interacts directly with importin β1 for non-classical nuclear import

Abstract

The latency-associated nuclear antigens (LANA) of KSHV and macaque RFHVMn, members of the RV1 rhadinovirus lineage, are closely related with conservation of complex nuclear localization signals (NLS) containing bipartite KR-rich motifs and RG-rich domains, which interact distinctly with importins α and ß1 for nuclear import via classical and non-classical pathways, respectively. RV1 LANAs are expressed in the nucleus of latently-infected cells where they inhibit replication and establish a dominant RV1 latency. Here we show that LANA homologs of macaque RRV and MneRV2 from the more distantly-related RV2 lineage, lack the KR-rich NLS, and instead have a large RG-rich NLS with multiple RG dipeptides and a conserved RGG motif. The RG-NLS interacts uniquely with importin β1, which mediates nuclear import and accumulation of RV2 LANA in the nucleolus. The alternative nuclear import and localization of RV2 LANA homologs may contribute to the dominant RV2 lytic replication phenotype. - Highlights: • LANA homologs of RRV and MneRV2 rhadinoviruses contain an N-terminal RGG/RG NLS. • The RGG/RG NLS motifs of RV2 LANA homologs interact with importin beta1. • RV2 LANAs are imported to the nucleus and nucleolus via the non-classical pathway.

Authors:
 [1];  [2];  [1];  [2];  [1];  [2];  [1];  [2]
  1. Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
22722975
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 511; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
73 NUCLEAR PHYSICS AND RADIATION PHYSICS; 60 APPLIED LIFE SCIENCES; IMPORTS; NUCLEI; SIGNALS

Citation Formats

Howard, Kellie, Department of Global Health, University of Washington, Seattle, WA, Cherezova, Lidia, Department of Global Health, University of Washington, Seattle, WA, DeMaster, Laura K., E-mail: laura.demaster@junotherapeutics.com, Department of Global Health, University of Washington, Seattle, WA, Rose, Timothy M., E-mail: timothy.rose@seattlechildrens.org, and Department of Pediatrics, University of Washington, Seattle, WA. ORF73 LANA homologs of RRV and MneRV2 contain an extended RGG/RG-rich nuclear and nucleolar localization signal that interacts directly with importin β1 for non-classical nuclear import. United States: N. p., 2017. Web. doi:10.1016/J.VIROL.2017.08.029.
Howard, Kellie, Department of Global Health, University of Washington, Seattle, WA, Cherezova, Lidia, Department of Global Health, University of Washington, Seattle, WA, DeMaster, Laura K., E-mail: laura.demaster@junotherapeutics.com, Department of Global Health, University of Washington, Seattle, WA, Rose, Timothy M., E-mail: timothy.rose@seattlechildrens.org, & Department of Pediatrics, University of Washington, Seattle, WA. ORF73 LANA homologs of RRV and MneRV2 contain an extended RGG/RG-rich nuclear and nucleolar localization signal that interacts directly with importin β1 for non-classical nuclear import. United States. doi:10.1016/J.VIROL.2017.08.029.
Howard, Kellie, Department of Global Health, University of Washington, Seattle, WA, Cherezova, Lidia, Department of Global Health, University of Washington, Seattle, WA, DeMaster, Laura K., E-mail: laura.demaster@junotherapeutics.com, Department of Global Health, University of Washington, Seattle, WA, Rose, Timothy M., E-mail: timothy.rose@seattlechildrens.org, and Department of Pediatrics, University of Washington, Seattle, WA. Wed . "ORF73 LANA homologs of RRV and MneRV2 contain an extended RGG/RG-rich nuclear and nucleolar localization signal that interacts directly with importin β1 for non-classical nuclear import". United States. doi:10.1016/J.VIROL.2017.08.029.
@article{osti_22722975,
title = {ORF73 LANA homologs of RRV and MneRV2 contain an extended RGG/RG-rich nuclear and nucleolar localization signal that interacts directly with importin β1 for non-classical nuclear import},
author = {Howard, Kellie and Department of Global Health, University of Washington, Seattle, WA and Cherezova, Lidia and Department of Global Health, University of Washington, Seattle, WA and DeMaster, Laura K., E-mail: laura.demaster@junotherapeutics.com and Department of Global Health, University of Washington, Seattle, WA and Rose, Timothy M., E-mail: timothy.rose@seattlechildrens.org and Department of Pediatrics, University of Washington, Seattle, WA},
abstractNote = {The latency-associated nuclear antigens (LANA) of KSHV and macaque RFHVMn, members of the RV1 rhadinovirus lineage, are closely related with conservation of complex nuclear localization signals (NLS) containing bipartite KR-rich motifs and RG-rich domains, which interact distinctly with importins α and ß1 for nuclear import via classical and non-classical pathways, respectively. RV1 LANAs are expressed in the nucleus of latently-infected cells where they inhibit replication and establish a dominant RV1 latency. Here we show that LANA homologs of macaque RRV and MneRV2 from the more distantly-related RV2 lineage, lack the KR-rich NLS, and instead have a large RG-rich NLS with multiple RG dipeptides and a conserved RGG motif. The RG-NLS interacts uniquely with importin β1, which mediates nuclear import and accumulation of RV2 LANA in the nucleolus. The alternative nuclear import and localization of RV2 LANA homologs may contribute to the dominant RV2 lytic replication phenotype. - Highlights: • LANA homologs of RRV and MneRV2 rhadinoviruses contain an N-terminal RGG/RG NLS. • The RGG/RG NLS motifs of RV2 LANA homologs interact with importin beta1. • RV2 LANAs are imported to the nucleus and nucleolus via the non-classical pathway.},
doi = {10.1016/J.VIROL.2017.08.029},
journal = {Virology},
issn = {0042-6822},
number = ,
volume = 511,
place = {United States},
year = {2017},
month = {11}
}