A chimeric human immunodeficiency virus type 1 (HIV-1) minimal Rev response element-ribozyme molecule exhibits dual antiviral function and inhibits cell-cell transmission of HIV-1 - PubMed (original) (raw)

A chimeric human immunodeficiency virus type 1 (HIV-1) minimal Rev response element-ribozyme molecule exhibits dual antiviral function and inhibits cell-cell transmission of HIV-1

O Yamada et al. J Virol. 1996 Mar.

Abstract

We have previously shown that hairpin ribozymes targeting the human immunodeficiency virus (HIV) genome can effectively inhibit virus replication in a variety of primary and cultured hematopoietic cells. To further increase antiviral potency and minimize the chance of viral resistance, we have now cloned the stem-loop II sequences of the HIV type 1 Rev response element into ribozyme transcription cassettes. Fusion RNA molecules were shown to function both as RNA decoys and ribozymes. Stable Molt-4/8 cell lines expressing fusion RNA of stem-loop II and a ribozyme directed at the HIV-type 1 U5 sequence (MSLMJT) or its disabled counterpart (MSLdMJT) were generated. The expression of fusion RNA was persistent for at least 6 months without apparent cytotoxicity. When virus inhibition was examined after the cocultivation of transduced cells with chronically infected Jurkat cells, much greater protection was observed in MSLMJT cells than in MSLdMJT or MMJT (expressing only the ribozyme) cells. Furthermore, to specifically compare the ribozyme activities in various transduced cells, we determined the quantitative levels of proviral DNA in the first round of virus replication (7 h after infection with HXB2). By competitive PCR, the proviral DNA levels in MSLMJT and MMJT cells were found to be reduced to 1/7 and 1/3, respectively, compared with those in MSLdMJT and MdMJT cells. These results suggest not only that the greater inhibition afforded by this fusion RNA was due to its function both as decoy and ribozyme but also that the ribozyme activity may be facilitated.

PubMed Disclaimer

Cited by

Bone Marrow Gene Therapy for HIV/AIDS.
Herrera-Carrillo E, Berkhout B. Herrera-Carrillo E, et al. Viruses. 2015 Jul 17;7(7):3910-36. doi: 10.3390/v7072804. Viruses. 2015. PMID: 26193303 Free PMC article. Review.
A branched DNA signal amplification assay for quantification of nucleic acid targets below 100 molecules/ml.
Collins ML, Irvine B, Tyner D, Fine E, Zayati C, Chang C, Horn T, Ahle D, Detmer J, Shen LP, Kolberg J, Bushnell S, Urdea MS, Ho DD. Collins ML, et al. Nucleic Acids Res. 1997 Aug 1;25(15):2979-84. doi: 10.1093/nar/25.15.2979. Nucleic Acids Res. 1997. PMID: 9224596 Free PMC article.
Inhibition of transcription by the TAR RNA of HIV-1 in a nuclear extract of HeLa cells.
Yamamoto R, Koseki S, Ohkawa J, Murakami K, Nishikawa S, Taira K, Kumar PK. Yamamoto R, et al. Nucleic Acids Res. 1997 Sep 1;25(17):3445-50. doi: 10.1093/nar/25.17.3445. Nucleic Acids Res. 1997. PMID: 9254702 Free PMC article.
A ribozyme targeted to cleave the polymerase gene sequences of different foot-and-mouth disease virus (FMDV) serotypes.
Stram Y, Molad T. Stram Y, et al. Virus Genes. 1997;15(1):33-7. doi: 10.1023/a:1007954830070. Virus Genes. 1997. PMID: 9354267
Multigene antiviral vectors inhibit diverse human immunodeficiency virus type 1 clades.
Gervaix A, Li X, Kraus G, Wong-Staal F. Gervaix A, et al. J Virol. 1997 Apr;71(4):3048-53. doi: 10.1128/JVI.71.4.3048-3053.1997. J Virol. 1997. PMID: 9060665 Free PMC article.

References

1. Cell. 1986 Sep 12;46(6):807-17 - PubMed
1. Virology. 1994 Nov 15;205(1):121-6 - PubMed
1. Science. 1988 Jan 15;239(4837):295-7 - PubMed
1. Nature. 1989 Mar 16;338(6212):254-7 - PubMed
1. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9 - PubMed

A chimeric human immunodeficiency virus type 1 (HIV-1) minimal Rev response element-ribozyme molecule exhibits dual antiviral function and inhibits cell-cell transmission of HIV-1 - PubMed (original) (raw)