Immune response to intermediate filament-associated, Epstein-Barr virus-induced early antigen

A murine monoclonal antibody (MAb) (15TD3) was found to recognize a unique filamentous structure in Epstein-Barr virus (EBV)-producing lymphoblastoid cell lines. By immunofluorescent morphology, in comparison with a control MAb to vimentin, the 15TD3 filamentous structure was judged to be associated with intermediate filaments of the cytoskeleton. Expression of the 15TD3 antigen and vimentin was induced simultaneously in some EBV genome-positive cell lines either by EBV superinfection or by 12-0-tetradecanoyl-1-phorbol-13-acetate (TPA) and n-butyrate treatment. The 15TD3 antigen was considered to be a restricted component of the EBV-induced early antigen (EA) complex. The 15TD3 antigen was expressed only in EBV genome-activated cells after either spontaneous EBV genome activation, EBV superinfection, or TPA and n-butyrate treatment. The expression of 15TD3 antigen paralleled the induction of EA in several models of induction of EBV antigens, and was detected only in EA+ cells which were stained with anti-EA+ human sera. The reactivity of 15TD3 MAb was blocked with anti-EA+ human serum, but not with anti-EA- serum. The synthesis of 15TD3 antigen was not inhibited with phosphonoacetic acid, was resistant to acetone fixation, and was sensitive to ethanol (or methanol) fixation. Human lymphoblastoid cells from patients with acute infectious mononucleosis were cloned for the production of antibodies which detected EBV-specific or -nonspecific epitopes on filamentous structures. Two human MAb were defined by two-color immunofluorescence to react to the 15TD3 determinants on intermediate filaments of EBV+ cells. This study supports the following views: that EBV genome activation induces a structure associated with intermediate filaments, and that antibodies against both the EBV-specific, intermediate filament-associated epitope and native intermediate filament epitopes are produced by some EBV-transformed lymphoblastoid cell lines from patients with infectious mononucleosis.