PMID- 2556717 OWN - NLM STAT- MEDLINE DCOM- 19900119 LR - 20190501 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 86 IP - 23 DP - 1989 Dec TI - Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. PG - 9558-62 AB - Epstein-Barr virus (EBV) efficiently transforms B lymphocytes to perpetual proliferation. The EBV laboratory strain P3HR-1 is transformation-incompetent and lacks a DNA segment that includes the EBV nuclear antigen 2 (EBNA-2) gene and a portion of the EBNA leader protein (EBNA-LP) gene. These two genes are expressed in transformed B lymphocytes. Recombinant transformation-competent EBVs were produced by transfecting P3HR-1-infected cells with a cosmid containing the DNA deleted in P3HR-1. Deletion of 105 nucleotides from the middle of the EBNA-2 gene had no discernible affect on transformation. Two larger EBNA-2 deletions abolished transformation but did not affect EBNA-2 nuclear localization. Two naturally occurring EBV variants (EBV types 1 and 2) differ extensively in their growth-transformation phenotype and in their EBNA-LP, EBNA-2, and EBNA-3A, -3B, and -3C genes. Recombinant P3HR-1 carrying EBV-1 EBNA-2 has many of the EBV-1 in vitro growth-transforming effects; recombinant P3HR-1, isogenic except for EBV-2 EBNA-2, has many of the EBV-2 growth-transforming effects including slow emergence of transformants, growth in tight clumps with few surrounding viable cells, and early sensitivity to dilution with fresh medium. Thus, EBNA-2 is an essential molecule in lymphocyte growth transformation by EBV and a major determinant of the differences between EBV-1 and EBV-2 in lymphocyte growth transformation. FAU - Cohen, J I AU - Cohen JI AD - Department of Medicine, Harvard Medical School, Boston, MA 02115. FAU - Wang, F AU - Wang F FAU - Mannick, J AU - Mannick J FAU - Kieff, E AU - Kieff E LA - eng GR - CA01395/CA/NCI NIH HHS/United States GR - CA01417/CA/NCI NIH HHS/United States GR - CA47006/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Antigens, Viral) RN - 0 (Epstein-Barr Virus Nuclear Antigens) RN - 0 (Viral Matrix Proteins) SB - IM MH - Antigens, Viral/*genetics/immunology MH - B-Lymphocytes/*immunology MH - Cell Line MH - Chromosome Deletion MH - Epstein-Barr Virus Nuclear Antigens MH - Genes, Viral MH - Herpesvirus 4, Human/genetics/*immunology MH - Humans MH - Immunoblotting MH - *Lymphocyte Activation MH - Plasmids MH - Viral Matrix Proteins/genetics PMC - PMC298536 EDAT- 1989/12/01 00:00 MHDA- 1989/12/01 00:01 PMCR- 1990/06/01 CRDT- 1989/12/01 00:00 PHST- 1989/12/01 00:00 [pubmed] PHST- 1989/12/01 00:01 [medline] PHST- 1989/12/01 00:00 [entrez] PHST- 1990/06/01 00:00 [pmc-release] AID - 10.1073/pnas.86.23.9558 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1989 Dec;86(23):9558-62. doi: 10.1073/pnas.86.23.9558.