Epstein-Barr virus replicative gene transcription during de novo infection of human thymocytes: simultaneous early expression of BZLF-1 and its repressor RAZ.
Epstein-Barr virus (EBV) is known to infect B cells and epithelial cells. We and others have shown that EBV can also infect a subset of thymocytes. Infection of thymocytes was accompanied by the appearance of linear EBV genome within 8 hr of infection. Circularization of the EBV genome was not detected. This is in contrast to the infection in B cells where the genome can circularize within 24 hr of infection. The appearance of the BamHI ZLF-1 gene product, ZEBRA, by RT-PCR, was observed within 8 hr of infection. The appearance of a novel fusion transcript (RAZ), which comprised regions of the BZLF-1 locus and the adjacent BRLF-1 locus, was detected by RT-PCR. ZEBRA protein was also identified in infected thymocytes by immunoprecipitation. In addition, we demonstrated that the EBNA-1 gene in infected thymocytes was transcribed from the Fp promoter, rather than from the Cp/Wp promoter which is used in latently infected B cells. Transcripts encoding gp350/220, the major coat protein of EBV, were identified, but we did not find any evidence of transcription from the LMP-2A or EBER-1 loci in infected thymocytes. These observations suggest that de novo EBV infection of thymocytes differs from infection of B cells. The main difference is that with thymocytes, no evidence could be found that the virus ever circularizes. Rather, EBV remains in a linear configuration from which replicative genes are transcribed.
Kelleher
C A
CA
Department of Pediatrics, National Jewish Center for Immunology, Denver, Colorado 80206, USA.
Paterson
R K
RK
Dreyfus
D H
DH
Streib
J E
JE
Xu
J W
JW
Takase
K
K
Jones
J F
JF
Gelfand
E W
EW
D000956:Antigens, Viral / Q000096:biosynthesis; D002478:Cells, Cultured; D004279:DNA, Viral / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D019309:Epstein-Barr Virus Nuclear Antigens; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D005814:Genes, Viral / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology*; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000096:biosynthesis*; D017735:Virus Latency / Q000235:genetics; D014779:Virus Replication / Q000235:genetics*
D000956:Antigens, Viral; C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins