AEGiS-05CROI: Trans complementation of integrase function.

5th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 1-5, 1998



Trans complementation of integrase function.

Conf Retroviruses Opportunistic Infect 1998 Feb 1-5; 5th:84 (abstract no. 31)

Soares MA, Weng Z, Wakefield J, Mcphearson S, Shaw GM, Leavitt AD, Boeke JD, Hahn BH; University of Alabama, Birmingham, AL.

Proviral integration is essential for HIV-1 replication and represents an important potential target for antiviral drug design. To study IN function in the context of infectious virions, we have developed a novel experimental system in which IN-mutant HIV-1 molecular clones are complemented in trans by Vpr-IN fusion proteins. Using this approach, we found that (i) Vpr-linked IN is efficiently packaged into virions independent of the Gag-Pol polyprotein, (ii) fusion proteins containing a natural RT/IN processing site are cleaved by the viral protease and (iii) only the cleaved IN protein complements IN-defective HIV-1 efficiently. We also showed that Vpr-mediated packaging restored IN function to a wide variety of IN-deficient HIV-I strains, including zinc finger, catalytic core and C-terminal domain mutants as well as viruses from which IN was completely deleted. Finally, we demonstrated that in vivo intragenic complementation between IN mutants defective in different protein domains was possible. More recently, we have begun to explore this trans complementation approach for its utility to target IN to selected sites in the genome. We have generated a panel of IN fusion proteins and investigated whether IN requires specific N- or C-terminal sequences (or structures) for its function in the virus particle. Preliminary data suggests that C-terminal IN fusions can retain complementation activity, albeit at a reduced level. Data from additional fusion constructs, including ones with DNA binding proteins, will be presented.

Keywords: AEGIS, Integrase, Gene Products, gag, HIV Protease, HIV-1, Virion, HIV-1 Reverse Transcriptase, Virus Replication, HIV, HIV Protease Inhibitors, HIV Infections, physiology, virology, AIDSKWDaegis,integrase,geneproducts,gag,hivprotease,hiv-1,virion,hiv-1reversetranscriptase,virusreplication,hiv,hivproteaseinhibitors,hivinfections,physiology,virology,aids

1998-02-01
31

Copyright © 1998 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.