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 following points were established: 1) productive infection with HHV-7 was required to obtain persistent down-modulation of surface CD4 (CD4(SURF)); 2) at 6 to 9 days postinfection, when approximately 50 to 60% of SupT1 cells still showed a CD4(SURF) dim positivity, a drastic loss of total CD4 protein was found by either Western blot or immunoprecipitation experiments; 3) a block in CD4 protein production was demonstrated by a radioimmunoprecipitation assay; 4) analysis of the mRNA steady-state levels and transfection studies performed with a plasmid containing the CD4 promoter/enhancer regions in front of the luciferase gene indicated that HHV-7 infection has a suppressive effect on CD4 transcription; 5) both CD4(SURF) and intracellular CD4 (CD4(INTRA)) were reduced 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(INTRA) co-localized with HHV-7 Ags within the same subcellular compartments of infected cells; and 7) the total amount of the tyrosine kinase p56(lck) and tyrosine phosphorylated p56(lck) levels were unchanged in HHV-7-infected versus uninfected cells.