Specific inhibition of human immunodeficiency virus type 1 replication by RNA transcribed in sense and antisense orientation from the 5′-leader/gag region

Georg Sczakiel*, MICHAEL PAWLITA, Andreas Kleinheinz

*Korrespondierende/r Autor/-in für diese Arbeit
38 Zitate (Scopus)

Abstract

The inhibitory effects of expression plasmids on HIV-1 replication were studied in a transient assay system. Test plasmids were co-microinjected with non-defective proviral HIV-1 DNA into a colon-carcinoma cell line (SW480) and the resulting infectious HIV-1 was quantitated after amplification in cocultivated CD4+ MT-4 cells. At a molar ratio of 1:1 and 5:1 plasmids capable of expressing a 410 bp HIV-1 fragment as antisense or sense transcript respectively both specifically inhibited HIV-1 replication up to 70%. This effect was specific for HIV-1 sequences and was not observed upon expression of unrelated RNA-segments. At a molar excess equal to or greater than 15:1, additional inhibitory effects were seen with control plasmids carrying only the strong human cytomegalovirus immediate early (HCMV IE) promoter/enhancer element. The reasons for these findings are discussed.

OriginalspracheEnglisch
ZeitschriftBiochemical and Biophysical Research Communications
Jahrgang169
Ausgabenummer2
Seiten (von - bis)643-651
Seitenumfang9
ISSN0006-291X
DOIs
PublikationsstatusVeröffentlicht - 15.06.1990

Fördermittel

We thank H. xur Hausen and L. Giimann for stimulating discussions and continuous encouragement. We also thank M. Martin for providing HIV-l proviral clone pNL4-3, R.C. GaIIo for HIV-l clone pBH10, H.-P. Vosberg for plasmid pHIV410 and H. Stijppler for plasmid pCMV-CAT. We thank A. Henn and H. G6txmann for excellent technical assistance and V. Bosch and H.-G. Rrgusslich for criticaIIy reading this manuscript. This work was supported by BMFf grant FKZ B-083-89.

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