Early events in Epstein-Barr virus infection of human B lymphocytes.
The sequence of Epstein-Barr virus (EBV) and B lymphocyte changes in the 3 days following acute infection was analyzed. By 16 hr the average infected lymphocyte had 1 EBV episome. Nuclear protein-2 (EBNA-2) and EBNA-leader protein (-LP) were detected by 12 hr, and by 32 hr were at the levels of stable EBV infection in lymphoblastoid cell lines (LCLs). At 12 hr, all EBNA-LP and EBNA-2 RNAs were initiated from the Pw promoter. By 36 hr a significant EBNA-LP and EBNA-2 RNA fraction initiated from the upstream Pc promoter. Throughout acute infection, a similar fraction of potentially bicistronic EBNA-LP mRNAs had first exon splices which would result in EBNA-LP translation. By 36 hr c-myc RNA was transiently induced, and CD21 and CD23 RNAs were beginning to increase. This coincided with low-level EBNA-1, EBNA-3A, B, and C, and latent membrane protein-1 (LMP-1) expression. By 46 hr, EBNA-1, the EBNA-3s, and LMP-1 were near the levels ordinarily found in LCLs and a substantial fraction of lymphocytes were in S phase. These results are compatible with a key role for EBNA-2 (or EBNA-LP) in regulating virus and cell gene expression. High-level expression of the EBV-encoded small RNAs, EBERs, was delayed beyond 36 hr and may, therefore, be activated by other virus or cell genes. A 65-kDa virion protein persisted in acutely infected cells. This protein could be a mediator of virus or cell gene expression.
Alfieri
C
C
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.
Birkenbach
M
M
Kieff
E
E
D000956:Antigens, Viral / Q000235:genetics*; D001402:B-Lymphocytes / Q000382:microbiology*; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000382:microbiology*; D004279:DNA, Viral / Q000096:biosynthesis; D019309:Epstein-Barr Virus Nuclear Antigens; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; D004279:DNA, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D012333:RNA, Messenger