ArticleProceedings of the National Academy of Sciences of the United States of America1997
Development of a novel anti-HIV-1 agent from within: effect of chimeric Vpr-containing protease cleavage site residues on virus replication.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 34 citations in OpenAlex.
- The HIV-1 Vpr Protein: A Multifaceted Target for Therapeutic Intervention.International journal of molecular sciences · 2017Review
- Capsid-Targeted Viral Inactivation: A Novel Tactic for Inhibiting Replication in Viral Infections.Viruses · 2016Review
- Nanotechnology-based approaches for the development of diagnostics, therapeutics, and vaccines.Monoclonal antibodies in immunodiagnosis and immunotherapy · 2014Review
- Efficient gene targeting mediated by a lentiviral vector-associated meganuclease.Nucleic acids research · 2011Article
- A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells.Nucleic acids research · 2010Article
- trans-Complementation rescue of cyclophilin A-deficient viruses reveals that the requirement for cyclophilin A in human immunodeficiency virus type 1 replication is independent of its isomerase activity.Journal of virology · 2002Article
- Functional role of residues corresponding to helical domain II (amino acids 35 to 46) of human immunodeficiency virus type 1 Vpr.Journal of virology · 2000Article
- Comparison of human immunodeficiency virus type 1 Pr55(Gag) and Pr160(Gag-pol) processing intermediates that accumulate in primary and transformed cells treated with peptidic and nonpeptidic protease inhibitors.Antimicrobial agents and chemotherapy · 2000Article
- HIV-1 Vpr-chloramphenicol acetyltransferase fusion proteins: sequence requirement for virion incorporation and analysis of antiviral effect.Gene therapy · 1999Article
- Gene therapy for HIV infections: Intracellular immunization.The Canadian journal of infectious diseases = Journal canadien des maladies infectieuses · 1999Article
- HIV-1 Gag shares a signature motif with annexin (Anx7), which is required for virus replication.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
- Production of uninfectious human immunodeficiency virus type 1 containing viral protein R fused to a single-chain antibody against viral integrase.Journal of virology · 1998Article
- Virion-targeted viral inactivation of human immunodeficiency virus type 1 by using Vpr fusion proteins.Journal of virology · 1998Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Effective antiviral agents will be of great value in controlling virus replication and delaying the onset of HIV-1-related disease symptoms. Current therapy involves the use of antiviral agents that target the enzymatic functions of the virus, resulting in the emergence of resistant viruses to these agents, thus lowering their effectiveness. To overcome this problem, we have considered the idea of developing novel agents from within HIV-1 as inhibitors of virus replication. The specificity of the Vpr protein for the HIV-1 virus particle makes it an attractive molecule for the development of antiviral agents targeting the events associated with virus maturation. We have generated chimeric Vpr proteins containing HIV-1-specific sequences added to the C terminus of Vpr. These sequences correspond to nine cleavage sites of the Gag and Gag-Pol precursors of HIV-1. The chimeric Vpr constructs were introduced into HIV-1 proviral DNA to assess their effect on virus infectivity using single- and multiple-round replication assays. The virus particles generated exhibited a variable replication pattern depending on the protease cleavage site used as a fusion partner. Interestingly, the chimeric Vpr containing the cleavage sequences from the junction of p24 and p2, 24/2, completely abolished virus infectivity. These results show that chimeric proteins generated from within HIV-1 have the ability to suppress HIV-1 replication and make ideal agents for gene therapy or intracellular immunization to treat HIV-1 infection.
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