Quantitative evaluation of the role of Epstein-Barr virus immediate-early protein BZLF1 in B-cell transformation.
The Epstein-Barr virus (EBV) immediate-early transactivator BZLF1 plays a key role in switching EBV infection from the latent to the lytic form by stimulating the expression cascade of lytic genes; it also regulates the expression of several cellular genes. Recently, we reported that BZLF1 is expressed in primary human B cells early after EBV infection. To investigate whether this BZLF1 expression early after infection plays a role in the EBV-induced growth transformation of primary B cells, we generated BZLF1-knockout EBV and quantitatively evaluated its transforming ability compared with that of wild-type EBV. We found that the 50% transforming dose of BZLF1-knockout EBV was quite similar to that of wild-type EBV. Established lymphoblastoid cell lines (LCLs) harbouring BZLF1-knockout EBV were indistinguishable from LCLs harbouring wild-type EBV in their pattern of latent gene expression and in their growth in vitro. Furthermore, the copy numbers of EBV episomes were very similar in the LCLs harbouring BZLF1-knockout EBV and in those harbouring wild-type EBV. These data indicate that disrupting BZLF1 expression in the context of the EBV genome, and the resultant inability to enter lytic replication, have little impact on the growth of LCLs and the steady-state copy number of EBV episomes in established LCLs.
Katsumura
Koichi Ricardo
KR
Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Maruo
Seiji
S
Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Wu
Yi
Y
Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Kanda
Teru
T
Research Center for Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Takada
Kenzo
K
Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
D001402:B-Lymphocytes / Q000502:physiology*; D045744:Cell Line, Tumor; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D010957:Plasmids; D015534:Trans-Activators / Q000378:metabolism*; D017735:Virus Latency
C063676:BZLF1 protein, Herpesvirus 4, Human; D015534:Trans-Activators