B cell terminal differentiation factor XBP-1 induces reactivation of Kaposi's sarcoma-associated herpesvirus.
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.
Yu
Fuqu
F
Department of Molecular and Medical Pharmacology, University of California at Los Angeles, CHS23-120, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Feng
Jiaying
J
Harada
Josephine N
JN
Chanda
Sumit K
SK
Kenney
Shannon C
SC
Sun
Ren
R
D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D002460:Cell Line; D004261:DNA Replication / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism; D000071717:X-Box Binding Protein 1
D050976:Basic-Leucine Zipper Transcription Factors; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C118265:K8 protein, Human herpesvirus 8; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human