HUMAN-HERPESVIRUS-7 INDUCES THE DOWN-REGULATION OF CD4 ANTIGEN IN LYMPHOID T-CELLS WITHOUT A AFFECTING P56(LCK) LEVELS

In this study, we investigated the fate of the CD4 Ag during infection of CD4(+) T cells with the T lymphotrophic human herpesvirus 7 (HHV-7 ), using the SupT1 lymphoblastoid T cell line as a model system, The f ollowing points were established: 1) productive infection with HHV-7 w as required to obtain persistent down-modulation of surface CD4 (CD4(S URF)); 2) at 6 to 9 days postinfection, when approximately 50 to 60% o f SupT1 cells still showed a CD4(SURF) dim positivity, a drastic loss of total CD4 protein was found by either Western blot or immunoprecipi tation experiments; 3) a block in CD4 protein production was demonstra ted by a radioimmunoprecipitation assay; 4) analysis of the mRNA stead y-state levels and transfection studies performed with a plasmid conta ining the CD4 promoter/enhancer regions in front of the luciferase gen e indicated that HHV-7 infection has a suppressive effect on CD4 trans cription; 5) both CD4(SURF) and intracellular CD4 (CD4(INTRA)) were re duced in HHV-7-infected cells with respect to uninfected controls, but the loss of CD4(SURF) was snore dramatic than that of CD4(INTRA): 6) immunogold labeling and electron microscopy demonstrated that CD4(INTR A) co-localized with HHV-7 Ags within the same subcellular compartment s of infected cells; and 7) the total amount of the tyrosine kinase p5 6(lck) and tyrosine phosphorylated p56(lck) levels were unchanged in H HV-7-infected versus uninfected cells.