Interaction between HIV-1 Rev and integrase proteins: A basis for the development of anti-HIV peptides

Joseph Rosenbluh, Zvi Hayouka, Shoshana Loya, Aviad Levin, Ayelet Armon-Omer, Elena Britan, Amnon Hizi, Moshe Kotler, Assaf Friedler, Abraham Loyter

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Human immunodeficiency virus 1 (HIV-1) Rev and integrase (IN) proteins are required within the nuclei of infected cells in the late and early phases of the viral replication cycle, respectively. Here we show using various biochemical methods, that these two proteins interact with each other in vitro and in vivo. Peptide mapping and fluorescence anisotropy showed that IN binds residues 1-30 and 49-74 of Rev. Following this observation, we identified two short Rev-derived peptides that inhibit the 3′-end processing and strand-transfer enzymatic activities of IN in vitro. The peptides bound IN in vitro, penetrated into cultured cells, and significantly inhibited HIV-1 in multinuclear activation of a galactosidase indicator (MAGI) and lymphoid cultured cells. Real time PCR analysis revealed that the inhibition of HIV-1 multiplication is due to inhibition of the catalytic activity of the viral IN. The present work describes novel anti-HIV-1 lead peptides that inhibit viral replication in cultured cells by blocking DNA integration in vivo.

Original languageEnglish
Pages (from-to)15743-15753
Number of pages11
JournalJournal of Biological Chemistry
Issue number21
Publication statusPublished - 25 May 2007
Externally publishedYes

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