Abstract
The herpesvirus life cycle has two distinct phases: latency and lytic replication. The viral immediate early protein replication and transcription activator (RTA) plays a central role in mediating the balance between these two phases. Here, we demonstrate that a B cell terminal differentiation factor X-box binding protein 1 (XBP-1) can effectively initiates Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation by activating the RTA promoter, which results in the induction of other viral lytic transcripts. We also showed splicing of the XBP-1 mRNA which specifically occurs during B cell differentiation is critical in triggering KSHV reactivation. This work demonstrates the integration of KSHV reactivation mechanisms with host cell differentiation.
MeSH terms
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Basic-Leucine Zipper Transcription Factors / metabolism
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Cell Line
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DNA Replication / genetics
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DNA, Viral / genetics
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation
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Genes, Reporter / genetics
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Herpesvirus 8, Human / physiology*
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Humans
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Promoter Regions, Genetic / genetics
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Regulatory Factor X Transcription Factors
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Repressor Proteins / metabolism
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic / genetics
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Viral Proteins / metabolism
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X-Box Binding Protein 1
Substances
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Basic-Leucine Zipper Transcription Factors
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DNA, Viral
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DNA-Binding Proteins
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K8 protein, Human herpesvirus 8
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Regulatory Factor X Transcription Factors
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Repressor Proteins
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Trans-Activators
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Transcription Factors
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Viral Proteins
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X-Box Binding Protein 1
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XBP1 protein, human