Latency pattern of Epstein-Barr virus and methylation status in Epstein-Barr virus-associated hemophagocytic syndrome.
Expression of different panels of latent gene transcripts is controlled by usage of three distinct Epstein-Barr virus (EBV) nuclear antigen (EBNA) promoters (Wp, Cp, and Qp). EBV-associated hemophagocytic syndrome, which is often a fatal disease and generally occurs after primary EBV infection, is characterized by monoclonal or oligoclonal proliferation of EBV-infected T cells. The latency pattern and EBNA promoter (Wp, Cp, and Qp) usage in EBV-infected cells from three patients with EBV-associated hemophagocytic syndrome were examined by reverse transcription-polymerase chain reaction (PCR). Three samples from the patients expressed EBER, EBNA1, EBNA2, latent membrane protein (LMP)1, and LMP2A transcripts. The transcripts of EBNA1 were initiated from not only Wp/Cp but also Qp. Lytic cycle Fp-initiated EBNA1 and EBV lytic gene BZLF1 transcripts were not detected. The methylation statuses of three EBNA promoters in three patients with EBV-associated hemophagocytic syndrome and in two patients with infectious mononucleosis were also analyzed using bisulfite PCR analysis. Wp was hypermethylated, and Qp was unmethylated in both diseases. Cp was highly methylated in EBV-associated hemophagocytic syndrome, however, whereas Cp was almost unmethylated in infectious mononucleosis. These results suggest that there may be distinct EBV-infected cell populations in EBV-associated hemophagocytic syndrome, which exhibit different patterns of EBV latent gene expression. The methylation status in Cp and phenotype of EBV-infected cells may be critical differences in EBV-associated hemophagocytic syndrome and infectious mononucleosis.
Yoshioka
Mikio
M
Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
Kikuta
Hideaki
H
Ishiguro
Nobuhisa
N
Endo
Rika
R
Kobayashi
Kunihiko
K
D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002675:Child, Preschool; D019175:DNA Methylation; D004279:DNA, Viral / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D015616:Histiocytosis, Non-Langerhans-Cell / Q000097:blood / Q000378:metabolism / Q000821:virology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins; D013154:Spleen / Q000378:metabolism / Q000821:virology; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D014764:Viral Proteins; D017735:Virus Latency
D000956:Antigens, Viral; C063676:BZLF1 protein, Herpesvirus 4, Human; D002352:Carrier Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C402641:EBNA-2 protein, Human herpesvirus 4; C432687:EBNA1BP2 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D015534:Trans-Activators; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C067169:RPL22 protein, human