Epstein-Barr virus nuclear antigen leader protein induces expression of thymus- and activation-regulated chemokine in B cells.
Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) plays a critical role in transformation of primary B lymphocytes to continuously proliferating lymphoblastoid cell lines (LCLs). To identify cellular genes in B cells whose expression is regulated by EBNA-LP, we performed microarray expression profiling on an EBV-negative human B-cell line, BJAB cells, that were transduced by a retroviral vector expressing the EBV EBNA-LP (BJAB-LP cells) and on BJAB cells that were transduced with a control vector (BJAB-vec cells). Microarray analysis led to the identification of a cellular gene encoding the CC chemokine TARC as a novel target gene that was induced by EBNA-LP. The levels of TARC mRNA expression and TARC secretion were significantly up-regulated in BJAB-LP compared with BJAB-vec cells. Induction of TARC was also observed when a subline of BJAB cells was converted by a recombinant EBV. Among the EBV-infected B-cell lines with the latency III phenotype that were tested, the LCLs especially secreted significantly high levels of TARC. The level of TARC secretion appeared to correlate with the level of full-length EBNA-LP expression. These results indicate that EBV infection induces TARC expression in B cells and that EBNA-LP is one of the viral gene products responsible for the induction.
Kanamori
Mikiko
M
Department of Virology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
Watanabe
Shinya
S
Honma
Reiko
R
Kuroda
Masayuki
M
Imai
Shosuke
S
Takada
Kenzo
K
Yamamoto
Naoki
N
Nishiyama
Yukihiro
Y
Kawaguchi
Yasushi
Y
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D001483:Base Sequence; D002460:Cell Line; D002472:Cell Transformation, Viral; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D005814:Genes, Viral; D005822:Genetic Vectors; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
C106230:CCL17 protein, human; D054414:Chemokine CCL17; D019742:Chemokines, CC; D018076:DNA, Complementary; C402640:EBNA-LP protein, Human herpesvirus 4; D014764:Viral Proteins