Elliott Kieff

Summary Established (laboratory) strains and fresh isolates of herpes simplex virus from patients with skin and genital lesions were classified into four groups depending on their effects on the social interaction among infected hep-2 cells. The groups comprised strains causing (1) rounding of cells but no adhesion or fusion, (2) loose aggregation of rounded cells, (3) tight adhesion of rounded cells, and (4) fusion of cells into polykaryocytes. Protype strains from each group were found to differ with respect to immunologic specificity, buoyant density in CsCl solutions and stability at 4°.

The gene encoding latent-infection membrane protein 1 (LMP1) was specifically mutated in Epstein-Barr virus (EBV) recombinants by inserting a nonsense linker after codon 9 or codon 84 or into an intron 186 bp 3' to the latter insertion site. EBV recombinants with the LMP1 intron mutation were wild type for LMP1 expression and for growth transformation of primary B lymphocytes. In contrast, EBV recombinants with the mutations in the LMP1 open reading frame expressed N-terminally truncated crossreactive proteins and could initiate or maintain primary B-lymphocyte transformation only when wild-type LMP1 was provided in trans by a coinfecting, transformation-defective EBV, P3HR-1. These data indicate that LMP1 is essential for EBV-mediated transformation of primary B lymphocytes, that the first 43 amino acids are critical for LMP1's function, and that codon 44-initiated LMP1 does not have a dominant negative effect on transformation.