Human herpesvirus 7 induces the down-regulation of CD4 antigen in lymphoid T cells without affecting p56lck 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 (CD4SURF); 2) at 6 to 9 days postinfection, when approximately 50 to 60% of SupT1 cells still showed a CD4SURF 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 CD4SURF and intracellular CD4 (CD4INTRA) were reduced in HHV-7-infected cells with respect to uninfected controls, but the loss of CD4SURF was more dramatic than that of CD4INTRA; 6) immunogold labeling and electron microscopy demonstrated that CD4INTRA co-localized with HHV-7 Ags within the same subcellular compartments of infected cells; and 7) the total amount of the tyrosine kinase p56lck and tyrosine phosphorylated p56lck levels were unchanged in HHV-7-infected versus uninfected cells.
Secchiero
P
P
Institute of Human Virology, University of Maryland at Baltimore 21201, USA.
Gibellini
D
D
Flamand
L
L
Robuffo
I
I
Marchisio
M
M
Capitani
S
S
Gallo
R C
RC
Zauli
G
G
D000956:Antigens, Viral / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000821:virology; D002461:Cell Line, Transformed; D015536:Down-Regulation / Q000276:immunology*; D004742:Enhancer Elements, Genetic / Q000276:immunology; D017245:Foscarnet / Q000494:pharmacology; D006566:Herpesviridae Infections / Q000276:immunology / Q000378:metabolism; D016199:Herpesvirus 7, Human / Q000276:immunology*; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology; D019061:src-Family Kinases / Q000378:metabolism*
D000956:Antigens, Viral; D015704:CD4 Antigens; D008562:Membrane Glycoproteins; D009856:Oncogene Proteins, Viral; D019000:Phosphotyrosine; D017245:Foscarnet; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases