High level of surface CD4 prevents stable human immunodeficiency virus infection of T-cell transfectants.
CD4 is the principal receptor for the human immunodeficiency virus (HIV). We have isolated and studied CD4-expressing tumor cell clones made by expressing CD4 in the T-cell tumor line HSB. Two clones, one designated HSBCD4, a clone expressing low levels of CD4, and the other, HSB10xCD4, a high-expresser CD4+ clone, were studied for their ability to bind and replicate HIV. In contrast to many other CD4+ cells that down-modulate CD4 following HIV infection, the HSB10xCD4 clones continued to express high levels of surface CD4 following infection with HIV. Unlike infection of HSBCD4 or many other human CD4+ cells, HIV infection of HSB10xCD4 clone was short lived: p24 antigen, provirus, or coculturable virus was present for less than 14 days following infection with several strains of HIV-1 or with HIV-2. When infection was initiated by transfection of proviral DNA, high and low CD4 expressers initially produced p24 antigen at approximately the same level. However, high CD4 expressers produced coculturable virus only during the first few days following transfection, whereas low CD4 expressers transfected with HIV continued to produce virus beyond 6 weeks. Monoclonal antibody-mediated down-modulation of CD4 surface expression on HSB10xCD4 clones permitted these formerly HIV-resistant cells to become persistently infected with HIV. Thus, high concentrations of CD4 on the surface of an HIV-infected cell prevent persistent HIV infection of CD4+ cells.
Marshall
W L
WL
Laboratory of Infectious Disease, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Diamond
D C
DC
Kowalski
M M
MM
Finberg
R W
RW
D001483:Base Sequence; D015704:CD4 Antigens / Q000502:physiology*; D015536:Down-Regulation; D005822:Genetic Vectors; D015726:Giant Cells / Q000382:microbiology; D006678:HIV / Q000254:growth & development* / Q000472:pathogenicity; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000254:growth & development / Q000472:pathogenicity; D015498:HIV-2 / Q000254:growth & development / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology*; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014774:Virulence; D014779:Virus Replication / Q000502:physiology*
D015704:CD4 Antigens; D016655:HIV Core Protein p24