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PMID: 15827179 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 replication and transcription activator regulates viral and cellular genes via interferon-stimulated response elements.

Journal of virology ·Vol. 79 ·No. 9 ·2005-05-00 ·Pages 5640-52

Zhang J, Wang J, Wood C, Xu D, Zhang L

Abstract

Kaposi's sarcoma-associated herpesvirus (also called human herpesvirus 8 [HHV-8]) replication and transcription activator (RTA) is apparently necessary and sufficient for the switch from viral latency to lytic replication. RTA may regulate open reading frame (ORF) K14 (viral OX-2 homologue) and ORF74 (viral G-protein-coupled receptor homologue) genes through an interferon-stimulated response element (ISRE)-like sequence (K14 ISRE) in the promoter region. RTA strongly activated a K14 ISRE-containing K14-ORF74 promoter reporter construct and a heterologous promoter reporter construct containing K14 ISRE. RTA could bind to K14 ISRE and other ISREs, activate promoter reporter constructs from interferon-simulated genes (ISGs), and selectively induce three endogenous ISGs in primary endothelial cells: ISG-54, myxovirus resistance protein 1 (MxA), and stimulated trans-acting factor of 50 kDa. In addition, a region in the RTA DNA-binding domain has been identified with certain sequence similarity to the DNA-binding domains of the interferon regulatory factor (IRF) family. Mutation in one conserved amino acid within this region reduced the ability of RTA to bind to ISRE as well as other RTA response elements. Furthermore, the mutant failed to activate RTA-responsive promoters and to induce viral lytic gene expression. The mutation at the same conserved amino acid residue in IRF-7 drastically reduced its ability to bind to DNA and to activate the beta interferon promoter. The sequence and functional similarities between RTA and IRFs suggest that the HHV-8 RTA may usurp the cellular IRF pathway.

MeSH Terms
Amino Acid Sequence Animals Antigens, CD Antigens, Surface/genetics DNA-Binding Proteins/genetics Gene Expression Regulation, Viral Herpesvirus 8, Human/physiology Humans Interferons/genetics,metabolism Molecular Sequence Data Open Reading Frames Promoter Regions, Genetic Response Elements/physiology Sequence Alignment Signal Transduction Trans-Activators/genetics,physiology Viral Proteins/genetics Virus Latency Virus Replication
Chemicals
Antigens, CD Antigens, Surface DNA-Binding Proteins K15 protein, Human herpesvirus 8 Trans-Activators Viral Proteins Interferons antigens, CD200
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zhang Jun
Nebraska Center for Virology, University of Nebraska, 1901 Vine St., Lincoln, NE 68588, USA.
Wang Jinzhong
Wood Charles
Xu Dongsheng
Zhang Luwen
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.79.9.5640-5652.2005
Published
2005-05-00
Pages
5640-52
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1082735
Subset
IM
Grants
NCI NIH HHS · R01 CA075903 · United States
FIC NIH HHS · TW01492 · United States
NCRR NIH HHS · RR15635 · United States
NCI NIH HHS · CA75903 · United States
NCRR NIH HHS · P20 RR015635 · United States
External Links
PubMed source DOI: 10.1128/JVI.79.9.5640-5652.2005 PMC Full Text View journal details
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