Differentially expressed genes in HIV-1-infected macrophages following treatment with the virus-suppressive immunomodulator murabutide.
The synthetic immunomodulator murabutide has been found to suppress human immunodeficiency virus type-1 (HIV-1) replication, in macrophages, through a regulated expression of cellular factors needed at different steps in the virus replication cycle. To identify cellular genes implicated in the murabutide-induced virus inhibition, we have carried out a differential display analysis on HIV-1-infected macrophages that were treated, or not, with murabutide. Sequencing of the differentially regulated cDNA bands and verification of the reproducibility of the murabutide effects, by reverse transcription-polymerase chain reaction or by Northern blotting, revealed an up-regulated expression of 21 genes and a down-regulation of seven others. The murabutide-regulated genes encoded proteins implicated in DNA binding, regulation of transcription, oxidative stress, metal binding, and other physiological functions. Six of the genes corresponded to unassigned/expressed sequence tags with yet unknown function. Among the genes which were up-regulated by murabutide and with established effects on inhibiting virus transcription, was the octamer binding factor 1 (Oct-1). We demonstrate the ability of murabutide to induce enhanced Oct-1 protein expression and DNA-binding activity in macrophages. Furthermore, our findings suggest the potential implication of additional transcription factors and metal-binding proteins in mediating the inhibitory effect of murabutide on virus transcription.
Truong
Marie José
MJ
Laboratory of Molecular Immunology of Infection and Inflammation, Pasteur Institute in Lille, 1 Rue du Pr Calmette, BP 245, Lille Cedex 59019, France.
Delsart
Véronique
V
Bahr
George M
GM
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D018929:Cell Culture Techniques; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D015497:HIV-1 / Q000254:growth & development*; D051863:Host Cell Factor C1; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000821:virology*; D050811:Octamer Transcription Factor-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D019380:Anti-HIV Agents; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D014157:Transcription Factors; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C033575:murabutide