Viral interleukin 10 is critical for the induction of B cell growth transformation by Epstein-Barr virus

• Published in: The Journal of experimental medicine Vol. 178; no. 2; pp. 439 - 447
• Main Authors: MIYAZAKI, I, CHEUNG, R. K, DOSCH, H.-M
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.08.1993; The Rockefeller University Press
• Subjects: B-Lymphocytes - microbiology; Base Sequence; Biological and medical sciences; Cell Transformation, Viral - genetics; Cell Transformation, Viral - physiology; Cells, Cultured; DNA; Epstein-Barr virus; Fundamental and applied biological sciences. Psychology; Gene Expression; Genes, Viral; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - physiology; Humans; Interleukin-10 - physiology; Microbiology; Molecular Sequence Data; Polymerase Chain Reaction; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; RNA, Messenger - metabolism; Virology; Gammaherpesvirinae; Human; Virus multiplication; Herpesviridae; B-Lymphocyte; Epstein Barr virus; Cell transformation; Host virus relation; Latency; Virus; Messenger RNA; Interleukin 10; Infected cell
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.178.2.439

We have used an efficient cDNA subtraction library procedure to identify newly induced genes in human B lymphocytes infected for 6 h with Epstein-Barr virus (EBV). Among the genes identified by automated sequencing of a random subset of clones from this library, one coded the EBV BCRF1 open reading frame, which specifies the viral interleukin 10 gene (vIL-10). This molecule is highly homologous to human (h)IL-10 and was previously thought to represent a "late" viral gene expressed only during the lytic phase of virus replication. Using gene amplification by reverse transcriptase polymerase chain reaction of B cell RNA obtained at varying times after infection, we detected vIL-10 expression within a few hours of EBV infection, followed, 20-30 h later by expression of hIL-10. Expression of both genes continued beyond the initial transformation phase (5-10 d) and was present in all transformed cell lines tested. When added at the time of viral infection, antisense (but not sense) oligonucleotides for vIL-10 mRNA (cytosolic half-life, approximately 6 h) prevented subsequent B cell transformation. The antisense effect was highly specific, leaving the expression levels of other transformation-related genes intact. Addition of exogenous (h)IL-10 rescued the transformation process in antisense-treated cells. Our observations establish vIL-10 as a new latency gene with a directly transformation-prerequisite function.