BZLF1
BZLF1 (BamHI Z fragment leftward open reading frame 1), also known as Zta, EB1, is an immediate-early viral gene of the Epstein–Barr virus (EBV) of the Herpes Virus Family, which induces cancers and infects primarily the B-cells of 95% of the human population.[1] This gene (along with others) produces the expression of other EBV genes in other stages of disease progression, and is involved in converting the virus from the latent to the lytic form.
ZEBRA protein
[edit]ZEBRA (BamHI Z Epstein-Barr virus replication activator, also known as Zta and BZLF1) is an early lytic protein of EBV encoded by BZLF1.
Structure
[edit]ZEBRA is a homodimer. Each subunit has 245 amino acid residues. It has a basic leucine zipper domain, a characteristic of many transcription factors.[2]
Function
[edit]Regulation of lytic replication
[edit]ZEBRA binds to the oriLyt (lytic origin of replication) of the EBV genome.[3] It acts as an essential transcriptional regulator that is required for wild-type levels of lytic DNA replication. Binding sites of ZEBRA are at the essential upstream component of oriLyt.[4] It interacts with the viral helicase-primase complex [5] and BMRF1,[6] the viral polymerase accessory factor.
Induction of DNA damage response
[edit]It has been shown to induce DNA damage response associated with the activation of EBV lytic cycle; the DNA damage response in turn allow maximal expression of lytic gene products, including ZEBRA itself and EA-D, the EBV DNA polymerase processivity factor.[7]
Research
[edit]BZLF1 expression level is used as an indicator for lytic EBV infection [8] BZLF1 transfection is also used to induce EBV viral production.[9]
References
[edit]- ^ "(-)-Epigallocatechin-3-gallate inhibition of Epstein–Barr virus spontaneous lytic infection involves ERK1/2 and PI3-K/Akt signaling in EBV-positive cells". Carcin.oxfordjournals.org. 2012-11-24. Archived from the original on 2014-01-27. Retrieved 2015-05-21.
- ^ Retrieved from http://biology.kenyon.edu/BMB/jsmol2013/ZEBRA_ALEXOLES_STEPHANIE_P/index.htm
- ^ Hammerschmidt, W. and Sugden, B. (2013). Replication of Epstein-Barr Viral DNA. Cold Spring Harbor Perspectives in Biology. Vol5, iss1.
- ^ Schepers, A.; Pich, D.; Hammerschmidt, W.(1993). Transcription factor with homology to the AP-1 family links RNA transcription and DNA replication in the lytic cycle of Epstein-Barr virus. EMBO Journal. Vol 12, iss 10.
- ^ El-Guindy et al. (2010).A subset of replication proteins enhances origin recognition and lytic replication by the Epstein-Barr virus ZEBRA protein. PLOS Pathogens. Vol 6, Iss 8.
- ^ Nakayama et al. (2009). Epstein-Barr virus polymerase processivity factor enhances BALF2 promoter transcription as a coactivator for the BZLF1 immediate-early protein. vol 284, iss 32.
- ^ Wang'ondu et al.(2015). DNA Damage Signaling Is Induced in the Absence of Epstein—Barr Virus (EBV) Lytic DNA Replication and in Response to Expression of ZEBRA. PLOS ONE.
- ^ Tsai et al. (2017). The biological properties of different Epstein-Barr virus strains explain their association with various types of cancers.
- ^ Kenney et al. (2017). Latent Membrane Protein 1 (LMP1) and LMP2A Collaborate To Promote Epstein-Barr Virus-Induced B Cell Lymphomas in a Cord Blood-Humanized Mouse Model but Are Not Essential. Journal of Virology. Volume 91. Issue 7. (see Materials and Methods: Production of infectious virus)