Trial of antisense RNA inhibition of HIV replication and gene expression

T. Shimada, H. Fujii, Bernhard Maier, S. Hayashi, H. Mitsuya, S. Broder, A. W. Nienhus

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We examined the feasibility of antisense RNA inhibition of human immunodeficiency virus (HIV) replication. In the first experiment we established CD4+ T-cell lines constitutively expressing various antisense HIV sequences using the retrovirus-mediated gene transfer technique. These cell lines were tested for their ability to withstand HIV de novo infection. In this challenge assay, however, we could not detect any significant difference in the survival rate between these genetically engineered cell lines and control T cells. In the second approach, the effects of antisense sequences on Tat expression were studied by monitoring the activities of reporter enzymes. A functional Tat expression vector and the antisense sequence expression vector were co-introduced into HeLa cells stably transfected with either the HIV-long terminal repeat (LTR) directed chloramphenicol acetyltransferase (CAT) or luciferase. Although the concentration of the antisense RNA was at least 10-fold higher than that of the sense Tat mRNA in cells, these antisense sequences could not inhibit transactivation of HIV-LTR. Regulation of HIV gene expression has proven to be very complicated and Tat transactivation of the HIV-LTR is extraordinarily strong. Consequently, it may be difficult to block HIV replication by the antisense strategy.

Original languageEnglish (US)
Pages (from-to)133-142
Number of pages10
JournalAntiviral Chemistry and Chemotherapy
Volume2
Issue number3
StatePublished - 1991
Externally publishedYes

Fingerprint

Antisense RNA
Virus Replication
HIV Long Terminal Repeat
HIV
Gene Expression
Cell Line
Transcriptional Activation
T-Lymphocytes
Gene Transfer Techniques
Chloramphenicol O-Acetyltransferase
Retroviridae
Luciferases
HeLa Cells
Messenger RNA
Enzymes
Infection

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

Shimada, T., Fujii, H., Maier, B., Hayashi, S., Mitsuya, H., Broder, S., & Nienhus, A. W. (1991). Trial of antisense RNA inhibition of HIV replication and gene expression. Antiviral Chemistry and Chemotherapy, 2(3), 133-142.

Trial of antisense RNA inhibition of HIV replication and gene expression. / Shimada, T.; Fujii, H.; Maier, Bernhard; Hayashi, S.; Mitsuya, H.; Broder, S.; Nienhus, A. W.

In: Antiviral Chemistry and Chemotherapy, Vol. 2, No. 3, 1991, p. 133-142.

Research output: Contribution to journalArticle

Shimada, T, Fujii, H, Maier, B, Hayashi, S, Mitsuya, H, Broder, S & Nienhus, AW 1991, 'Trial of antisense RNA inhibition of HIV replication and gene expression', Antiviral Chemistry and Chemotherapy, vol. 2, no. 3, pp. 133-142.
Shimada T, Fujii H, Maier B, Hayashi S, Mitsuya H, Broder S et al. Trial of antisense RNA inhibition of HIV replication and gene expression. Antiviral Chemistry and Chemotherapy. 1991;2(3):133-142.
Shimada, T. ; Fujii, H. ; Maier, Bernhard ; Hayashi, S. ; Mitsuya, H. ; Broder, S. ; Nienhus, A. W. / Trial of antisense RNA inhibition of HIV replication and gene expression. In: Antiviral Chemistry and Chemotherapy. 1991 ; Vol. 2, No. 3. pp. 133-142.
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