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

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

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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

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Virus Diseases
Virion
HIV-1
Lymphocytes
Peptides
Peptide Hydrolases
HIV Infections
Protease Inhibitors
Human immunodeficiency virus 1 p16 protease
Saquinavir
Viruses
gag Gene Products
Polyproteins
Limit of Detection
Bacteria

All Science Journal Classification (ASJC) codes

  • General

Cite this

Potash, Mary Jane ; Bentsman, Galina ; Muir, Thomas William ; Krachmarov, Chavdar ; Sova, Pavel ; Volsky, David J. / Peptide inhibitors of HIV-1 protease and viral infection of peripheral blood lymphocytes based on HIV-1 Vif. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 23. pp. 13865-13868.
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Peptide inhibitors of HIV-1 protease and viral infection of peripheral blood lymphocytes based on HIV-1 Vif. / Potash, Mary Jane; Bentsman, Galina; Muir, Thomas William; Krachmarov, Chavdar; Sova, Pavel; Volsky, David J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 23, 10.11.1998, p. 13865-13868.

Research output: Contribution to journalArticle

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AU - Potash, Mary Jane

AU - Bentsman, Galina

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