BZLF1BamHI Z Leftward reading Frame 1
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This virus was derived from a Chinese NPC patient and has shown high expression level of lytic genes such as BZLF1 and BALF in the M81-infected cells [43].
Several studies have also evidenced that lytic proteins such as BZLF1, BRLF1, and BRMF1 could be potential therapeutic targets but further investigations and validations are warranted [49, 55, 70].
Raji cell line models expressing EBV latent infection showed that H3K4me, H3K27me3, and H4K20me3 repress BZLF1 transcription, leading to reactivation of EBV [157].
Although EBV is not integrated into the host genome, its materials such as EBNA1 and BZLF1 seem to interact with various cellular promoters and induce epigenetic alterations that are associated with carcinogenesis.
Mauser et al., "Use of adenovirus vectors expressing Epstein-Barr virus (EBV) immediate-early protein BZLF1 or BRLF1 to treat EBV-positive tumors," Journal of Virology, vol.
Kuang, "BZLF1 attenuates transmission of inflammatory paracrine senescence in Epstein-Barr virus-infected cells by down-regulating tumor necrosis factor alpha," Journal of Virology, vol.
However, it includes CD8 T cell epitopes from other EBV early antigens, such as EBNA1, EBNA3, EBNA6, BMRF1, BRLF1, and BZLF1 (Tables 1 and 5).
Peptide ligands HLA-E* HLA-E* TCR CD94/ Reference (origin) 01:01 01:03 NKG2A Naturally presented ligands ALALVRMLI (ATP binding cassette ND ND ND + [18] transporter, MRP7) VMAPRTLFL + + - + [33] (HLA-G) VMAPRTLIL (CMV + + + + [26, 35, UL40; HLA-C) 38] VMAPRTLVL (CMV; + + + + [36, 57] HLA-A) Predicted ligands QMRPVSRVL + + ND - [17] (human HSP60) AISPRTLNA (HIV ND ND ND + [19] Gag protein) SQQPYLQLQ ND ND ND + [20] (gliadin- wheat protein) SQAPLPCVL (EBV- + + + + 33] BZLF1 protein) This table shows the diversity of naturally presented or predicted HLA-E peptide ligands and their interactions with immune receptors.
However, several groups have demonstrated that SLE patients have abnormally high expression of several viral mRNAs (coding for BZLF1, gp350, viral IL10, LMP1, LMP2, and EBNA1) [54, 59].
Contrarily, CD8+ cytotoxic T-cells specific for the two lytic cycle EBV antigens, BZLF1 and BMLF1, have been detected in synovial fluid and synovial membranes of RA patients, indicating a contribution of infiltrated cytotoxic T-cells specific for EBV lytic cycle antigens in joint inflammation [84, 85].
Eight out of 12 SS saliva samples were found to have an activating effect on the BZLF1 promoter in EBV-negative BZLFl-transfected salivary gland cells, indicating a possible frequent reactivation of EBV in the oropharynx of SS patients [96].
Function Protein EBNA1 EBNA-LP Latent state nuclear antigens EBNA2 EBNA3A EBNA3B EBNA3C gp350 gp42 Glycoproteins involved in viral entry BMRF2 gH gL gp110 gN gp150 Envelope proteins BILF2 BILF1 BDLF2 BZLF1 BRLF1 EA/D Initiation of lytic replication BSLF1 BBLF4 BBLF2/3 BALF5 BALF2 Viral IL10 BARF1 Immune evasion LF2 BNLF2a BMLF1/BSLF2 EA/R Antiapoptotic BALF1 LMP1 LMP2