Tags

Type your tag names separated by a space and hit enter

Inhibition of HIV-1 transcription and virus replication using soluble Tat peptide analogs.
Virology. 1997 Jan 20; 227(2):431-8.V

Abstract

The human immunodeficiency virus type 1 (HIV-1) transactivator Tat protein is essential for efficient viral gene expression and virus replication. The Tat core domain, a stretch of 12 amino acids between the cysteine-rich and the basic domain, is conserved in all HIV isolates and required for interaction with a number of cellular transcriptional regulatory proteins. Here we demonstrate that soluble peptide analogs of the Tat core domain (amino acid 36-50) are able to effectively block LTR transactivation. In transfection experiments, Tat core peptide analogs containing amino acid substitutions at position 41 and 44 inhibited Tat transactivation of an HIV-1 LTR-CAT reporter construct up to 80-fold. In contrast, inhibition of other promoters such as HTLV-I and CMV was approximately 2-fold. Tat peptide analog 36-50 (41/44) inhibited HIV virus replication by 85% in latently infected U1 cells induced with Tat. Furthermore, U1 cells treated with the Tat peptide 36-50 (41/44) analog showed markedly delayed virus transmission when cocultivated with parental U937 cells. Interestingly, while both short and long peptide analogs (amino acids 36-50 vs 36-72) inhibited Tat transactivation in transient assays, the short peptides were more effective inhibitors of virus replication in U1 cells. The Tat peptide analog did not decrease expression of cellular genes including beta-actin, GAPDH, and histone H2B.

Authors+Show Affiliations

Laboratory of Molecular Virology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9018142

Citation

Kashanchi, F, et al. "Inhibition of HIV-1 Transcription and Virus Replication Using Soluble Tat Peptide Analogs." Virology, vol. 227, no. 2, 1997, pp. 431-8.
Kashanchi F, Sadaie MR, Brady JN. Inhibition of HIV-1 transcription and virus replication using soluble Tat peptide analogs. Virology. 1997;227(2):431-8.
Kashanchi, F., Sadaie, M. R., & Brady, J. N. (1997). Inhibition of HIV-1 transcription and virus replication using soluble Tat peptide analogs. Virology, 227(2), 431-8.
Kashanchi F, Sadaie MR, Brady JN. Inhibition of HIV-1 Transcription and Virus Replication Using Soluble Tat Peptide Analogs. Virology. 1997 Jan 20;227(2):431-8. PubMed PMID: 9018142.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of HIV-1 transcription and virus replication using soluble Tat peptide analogs. AU - Kashanchi,F, AU - Sadaie,M R, AU - Brady,J N, PY - 1997/1/20/pubmed PY - 1997/1/20/medline PY - 1997/1/20/entrez SP - 431 EP - 8 JF - Virology JO - Virology VL - 227 IS - 2 N2 - The human immunodeficiency virus type 1 (HIV-1) transactivator Tat protein is essential for efficient viral gene expression and virus replication. The Tat core domain, a stretch of 12 amino acids between the cysteine-rich and the basic domain, is conserved in all HIV isolates and required for interaction with a number of cellular transcriptional regulatory proteins. Here we demonstrate that soluble peptide analogs of the Tat core domain (amino acid 36-50) are able to effectively block LTR transactivation. In transfection experiments, Tat core peptide analogs containing amino acid substitutions at position 41 and 44 inhibited Tat transactivation of an HIV-1 LTR-CAT reporter construct up to 80-fold. In contrast, inhibition of other promoters such as HTLV-I and CMV was approximately 2-fold. Tat peptide analog 36-50 (41/44) inhibited HIV virus replication by 85% in latently infected U1 cells induced with Tat. Furthermore, U1 cells treated with the Tat peptide 36-50 (41/44) analog showed markedly delayed virus transmission when cocultivated with parental U937 cells. Interestingly, while both short and long peptide analogs (amino acids 36-50 vs 36-72) inhibited Tat transactivation in transient assays, the short peptides were more effective inhibitors of virus replication in U1 cells. The Tat peptide analog did not decrease expression of cellular genes including beta-actin, GAPDH, and histone H2B. SN - 0042-6822 UR - https://www.unboundmedicine.com/medline/citation/9018142/Inhibition_of_HIV_1_transcription_and_virus_replication_using_soluble_Tat_peptide_analogs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(96)98346-4 DB - PRIME DP - Unbound Medicine ER -