Volume : 4, Issue : 2, February - 2015

Negative Effect of Ascorbic Acid in Gene Regulation of Provirus Hiv-1

Takuma Hayashi

Abstract :

<p>To elucidate the inhibition mechanism of human immunodeficiency virus type 1 (HIV&ndash;1) replication by ascorbic acid, we have investigated and compared the effect of noncytoxic concentrations of ascorbic acid on provirus HIV&ndash;1 replication. Using trans&ndash;activator of transcription factor (tat) expressing cells or non&ndash;expressing cells transfected HIV&ndash;1&ndash;long terminal repeat (LTR) chloramphenicol acetyl transferase (CAT) plasmid, we examined the action of ascorbic acid on tat dependent transcriptional activation of HIV&ndash;1 gene through enhancer/promoter of HIV&ndash;1&ndash;LTR. In tat expressing cells, ascorbic acid strongly reduced the levels of intracellular CAT activity in a dose dependent manner (5 to 100 ?g/ml). Alternatively in non tat&ndash;expressing cells, CAT activity was reduced somewhat. Using other in vivo and in vitro experiments, ascorbic acid inhibited the activity of tat dependent HIV&ndash;1 RNA elongation, but did not inhibit activity of basal transcriptional activation of HIV&ndash;1 gene. The intracellular HIV&ndash;1 genome RNA patterns in ascorbic acid treated cells infected with HIV&ndash;1 showed significant differences in the synthesis and the processing of individual HIV&ndash;1 viral genome RNAs compared to the patterns of untreated controls. Tat dependent HIV&ndash;1 transcription was specifically reduced, because in contrast to HIV&ndash;1 transcription, transcriptional activities through adenovirus major late promoter, Rous sarcoma virus promoter or SV40 promoter were not reduced by treatment of ascorbic acid. Furthermore, the activation of transcription factors was not affected by treatment of ascorbic acid. These results show that ascorbic acid specifically inhibits the replication of HIV&ndash;1 on down&ndash;regulation of tat dependent HIV&ndash;1 genome RNA elongation</p>