C-C chemokine RANTES and HIV long terminal repeat-driven gene expression.
The C-C chemokines RANTES, MIP-1alpha, and MIP-1beta have been characterized as constituents of an HIV- and SIV-suppressive factor released by CD8+ cells. Furthermore, it has been demonstrated that chemokine receptors cooperate in HIV entry. However, these proteins are also known to have an effect on multiple intracellular signaling cascades that may affect the process of transcription. In the present study we demonstrate that treatment of CD4+ T cells with these chemokines or with cell supernatants from HTLV-I-immortalized CD8+ T cells results in significant reduction in the abundance of HIV-1-specific RNA as analyzed by Northern blot hybridization. To examine the possibility that such suppressive factors may inhibit HIV RNA transcription, we studied the effect of RANTES, the most effective HIV-suppressive chemokine, on basal and Tat-induced HIV-directed LTR expression of a reporter gene. Neither recombinant RANTES nor conditioned medium from CD8+ cells significantly altered HIV-1 LTR-directed chloramphenicol acetyltransferase expression in either transiently or stably transfected CD4+ T cell lines, either in the presence or in the absence of Tat. These results suggest that C-C chemokines do not inhibit viral RNA transcription.
Garzino-Demo
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A
Institute of Human Virology, Medical Biotechnology Center, University of Maryland Biotechnology Institute and School of Medicine, Baltimore 21201, USA.
Arya
S K
SK
Devico
A L
AL
Cocchi
F
F
Lusso
P
P
Gallo
R C
RC
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology; D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology* / Q000627:therapeutic use; D054410:Chemokine CCL7; D016207:Cytokines; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy; D016325:HIV Long Terminal Repeat / Q000187:drug effects* / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development; D015498:HIV-2 / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D019169:Jurkat Cells; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology / Q000627:therapeutic use; D018945:Monocyte Chemoattractant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000254:growth & development; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
C515450:CCL7 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D012367:RNA, Viral; D011994:Recombinant Proteins