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HIV‐1 associated down‐modulation of CD4 gene expression is differentially restricted in lymphocytic and monocytic cell lines
Author(s) -
Geleziunas R.,
Bour S.,
Wainberg M.A.
Publication year - 1994
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.55.5.589
Subject(s) - biology , jurkat cells , cell culture , gene expression , thp1 cell line , virus , microbiology and biotechnology , messenger rna , virology , viral replication , t cell , gene , immunology , immune system , genetics
We previously demonstrated that chronic infection of a monocytic cell line (U‐937) with human immunodeficiency virus type 1 (HIV‐1) was not accompanied by down‐modulation of CD4 transcription, unlike the situation with CD4 + T lymphocyte lines. To better understand the refractoriness of monocytes to alterations in levels of CD4 mRNA, we treated HIV‐III B chronically infected U‐937 cells with phorbol myristate acetate (PMA), a known stimulus of HIV gene expression. Although PMA caused a significant increase in HIV mRNA levels that was sustained over 7 days, no effect on CD4 transcript levels was noted. Clonal derivatives of HIV‐III B infected U‐937 cells, which produced a variety of infectious and defective particles, were likewise not affected in ability to produce CD4 mRNA. To rule out the possibility that U‐937 cells select out HIV‐1 variants unable to modulate CD4 mRNA levels, we passaged infectious virus from a U‐937 clonal derivative (UHC1) onto different monocytic and T lymphocytic cell lines. In monocytic cell lines (U‐937, PLB‐985, THP‐1), we observed an avirulent infection that did not affect CD4 mRNA levels, whereas UHC1 infection of each of two T lymphocytic cell lines (CEM‐T4, Jurkat) caused both cytopathic replication and reductions in GD4 mRNA levels. In one case (Jurkat), variants expressing low CD4 mRNA may have emerged, because the outgrowth no longer expressed viral products. In the other case (CEM‐T4), high expression of viral genes was accompanied by CD4 mRNA down‐modulation, suggesting either that low‐CD4‐expressing variants were selected that maintained viral gene expression or that CD4 gene expression was repressed by viral products. J. Leukoc. Biol. 55: 589–595; 1994.