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Kaposi's Sarcoma-Associated Herpesvirus-Encoded Latency-Associated Nuclear Antigen Modulates K1 Expression through Its cis -Acting Elements within the Terminal Repeats
- Source :
- Journal of Virology. 80:3445-3458
- Publication Year :
- 2006
- Publisher :
- American Society for Microbiology, 2006.
-
Abstract
- K1 is the first open reading frame encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) and lies positionally to the immediate right of the terminal repeats. K1 is a transmembrane glycoprotein having a functional immunoreceptor tyrosine-based activation motif (ITAM) capable of activating B-cell receptor signaling. K1 is expressed mostly during the lytic cycle of the virus and its promoter lies within the terminal repeat which contains the binding sites for latency-associated nuclear antigen (LANA). The K1 promoter (K1p) having LANA binding sites assayed by reporter assay demonstrated that LANA is capable of down-regulating K1 promoter transcriptional activity. However, the KSHV replication transcription activator RTA up-regulates K1p transcriptional activity. The promoter deleted of LANA binding sites showed loss in LANA-mediated down-regulation but was unaffected for RTA-mediated up-regulation. Increasing amounts of RTA rescued LANA-mediated repression of K1p transcriptional activity in cotransfection experiments. Reporter assay data suggest that LANA binding to its cognate sequence is critical for LANA-mediated repression of K1p as a LANA construct lacking the DNA binding domain was unable to repress K1p transcription. Additionally, KSHV primary infection experiments suggest that K1 is expressed during early infection but is repressed on the establishment of latency and so follows an expression profile similar to that of RTA during infection. Analysis of the promoter sequence revealed the presence of Oct-1 transcription factor binding sites within the −116 to +76 region. Mutational analysis of the Oct-1 sites abolished RTA-mediated transcriptional activation, suggesting that RTA up-regulates K1p transcription through binding to this transcription factor.
- Subjects :
- Gene Expression Regulation, Viral
viruses
Amino Acid Motifs
Blotting, Western
Molecular Sequence Data
Immunology
Electrophoretic Mobility Shift Assay
Biology
medicine.disease_cause
Models, Biological
Microbiology
Cell Line
Immediate-Early Proteins
Open Reading Frames
Viral Proteins
Genes, Reporter
Transcription (biology)
Cell Line, Tumor
Virology
medicine
Humans
Electrophoretic mobility shift assay
Amino Acid Sequence
Kaposi's sarcoma-associated herpesvirus
Binding site
Luciferases
Promoter Regions, Genetic
Antigens, Viral
Gene
Transcription factor
Glycoproteins
Binding Sites
Sequence Homology, Amino Acid
Terminal Repeat Sequences
Nuclear Proteins
virus diseases
DNA-binding domain
biochemical phenomena, metabolism, and nutrition
Molecular biology
Genome Replication and Regulation of Viral Gene Expression
DNA binding site
Insect Science
Herpesvirus 8, Human
Mutagenesis, Site-Directed
Trans-Activators
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 80
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....fc6770ee616128e74e059f16c63aaa61