Peptide inhibitors of HIV-1 protease and viral infection of peripheral blood lymphocytes based on HIV-1 Vif

Mary Jane Potash, Galina Bentsman, Tom Muir, Chavdar Krachmarov, Pavel Sova, David J. Volsky

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

We recently reported that HIV-1 Vif (virion infectivity factor) inhibits HIV-1 protease in vitro and in bacteria, suggesting that it may serve as the basis for the design of new protease inhibitors and treatment for HIV-1 infection. To evaluate this possibility, we synthesized peptide derivatives from the region of Vif, which inhibits protease, and tested their activity on protease. In an assay of cleavage of virion-like particles composed of HIV-1 Gag precursor polyprotein, full-length recombinant Vif, and a peptide consisting of residues 21-65 of Vif, but not a control peptide or BSA, inhibited protease activity. Vif(21-65) blocked protease at a molar ratio of two to one. We then tested this peptide and a smaller peptide, Vif(41-65), for their effects on HIV-1 infection of peripheral blood lymphocytes. Both Vif peptides inhibited virus expression below the limit of detection, but control peptides had no effect. To investigate its site of action, Vif(21- 65) was tested for its effect on Gag cleavage by protease during HIV-1 infection. We found that commensurate with its reduction of virus expression, Vif(21-65) inhibited the cleavage of the polyprotein p55 to mature p24. These results are similar to those obtained by using Ro 31-8959, a protease inhibitor in clinical use. We conclude that Vif-derived peptides inhibit protease during HIV-1 infection and may be useful for the development of new protease inhibitors.

Original languageEnglish (US)
Pages (from-to)13865-13868
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number23
DOIs
StatePublished - Nov 10 1998

All Science Journal Classification (ASJC) codes

  • General

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