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PMID: 11238851 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 mediates episome persistence through cis-acting terminal repeat (TR) sequence and specifically binds TR DNA.

Journal of virology ·Vol. 75 ·No. 7 ·2001-04-00 ·Pages 3250-8

Ballestas ME, Kaye KM

Abstract

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) (also known as human herpesvirus 8) latently infects KS tumors, primary effusion lymphomas (PELs), and PEL cell lines. In latently infected cells, KSHV DNA is maintained as circularized, extrachromosomal episomes. To persist in proliferating cells, KSHV episomes must replicate and efficiently segregate to progeny nuclei. In uninfected B-lymphoblastoid cells, KSHV latency-associated nuclear antigen (LANA1) is necessary and sufficient for persistence of artificial episomes containing specific KSHV DNA. In previous work, the cis-acting sequence required for episome persistence contained KSHV terminal-repeat (TR) DNA and unique KSHV sequence. We now show that cis-acting KSHV TR DNA is necessary and sufficient for LANA1-mediated episome persistence. Furthermore, LANA1 binds TR DNA in mobility shift assays and a 20-nucleotide LANA1 binding sequence has been identified. Since LANA1 colocalizes with KSHV episomes along metaphase chromosomes, these results are consistent with a model in which LANA1 may bridge TR DNA to chromosomes during mitosis to efficiently segregate KSHV episomes to progeny nuclei.

MeSH Terms
Antigens, Viral/physiology Base Sequence DNA Replication DNA, Viral/metabolism Herpesvirus 8, Human/genetics,immunology,physiology Molecular Sequence Data Nuclear Proteins/physiology Plasmids Precipitin Tests Terminal Repeat Sequences
Chemicals
Antigens, Viral DNA, Viral Nuclear Proteins latency-associated nuclear antigen
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ballestas M E
Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kaye K M
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.75.7.3250-3258.2001
Published
2001-04-00
Pages
3250-8
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC114118
Subset
IM
Grants
NCI NIH HHS · 5T32CA09031 · United States
NCI NIH HHS · R01 CA082036 · United States
NCI NIH HHS · CA67380 · United States
NCI NIH HHS · K01 CA085751 · United States
NCI NIH HHS · T32 CA009031 · United States
NCI NIH HHS · CA85751 · United States
External Links
PubMed source DOI: 10.1128/JVI.75.7.3250-3258.2001 PMC Full Text View journal details
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