Differential gene regulation by Epstein-Barr virus type 1 and type 2 EBNA2.
A transfection assay with a lymphoblastoid cell line infected with Epstein-Barr virus was used to compare the abilities of type 1 and type 2 EBNA2 to sustain cell proliferation. The reduced proliferation in cells expressing type 2 EBNA2 correlated with loss of expression of some cell genes that are known to be targets of type 1 EBNA2. Microarray analysis of EBNA2 target genes identified a small number of genes that are more strongly induced by type 1 than by type 2 EBNA2, and one of these genes (CXCR7) was shown to be required for proliferation of lymphoblastoid cell lines. The Epstein-Barr virus LMP1 gene was also more strongly induced by type 1 EBNA2 than by type 2, but this effect was transient. Type 1 and type 2 EBNA2 were equally effective at arresting cell proliferation of Burkitt's lymphoma cell lines lacking Epstein-Barr virus and were also shown to cause apoptosis in these cells. The results indicate that differential gene regulation by Epstein-Barr virus type 1 and type 2 EBNA2 may be the basis for the much weaker B-cell transformation activity of type 2 Epstein-Barr virus strains compared to type 1 strains.
Lucchesi
Walter
W
Department of Virology, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.
Brady
Gareth
G
Dittrich-Breiholz
Oliver
O
Kracht
Michael
M
Russ
Rainer
R
Farrell
Paul J
PJ
D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D054387:Receptors, CXCR / Q000096:biosynthesis; D014763:Viral Matrix Proteins / Q000096:biosynthesis; D014764:Viral Proteins / Q000378:metabolism*
C501896:ACKR3 protein, human; C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D054387:Receptors, CXCR; D014763:Viral Matrix Proteins; D014764:Viral Proteins