Journal article
Chimeric Cyanovirin-MPER Recombinantly Engineered Proteins Cause Cell-Free Virolysis of HIV-1
Antimicrobial agents and chemotherapy, v 57(10), pp 4743-4750
Oct 2013
PMID: 23856780
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Human immunodeficiency virus (HIV) is the primary etiologic agent responsible for the AIDS pandemic. In this work, we used a chimeric recombinant protein strategy to test the possibility of irreversibly destroying the HIV-1 virion using an agent that simultaneously binds the Env protein and viral membrane. We constructed a fusion of the lectin cyanovirin-N (CVN) and the gp41 membrane-proximal external region (MPER) peptide with a variable-length (Gly
4
Ser)
x
linker (where
x
is 4 or 8) between the C terminus of the former and N terminus of the latter. The His-tagged recombinant proteins, expressed in BL21(DE3)pLysS cells and purified by immobilized metal affinity chromatography followed by gel filtration, were found to display a nanomolar efficacy in blocking BaL-pseudotyped HIV-1 infection of HOS.T4.R5 cells. This antiviral activity was HIV-1 specific, since it did not inhibit cell infection by vesicular stomatitis virus (VSV) or amphotropic-murine leukemia virus. Importantly, the chimeric proteins were found to release intraviral p24 protein from both BaL-pseudotyped HIV-1 and fully infectious BaL HIV-1 in a dose-dependent manner in the absence of host cells. The addition of either MPER or CVN was found to outcompete this virolytic effect, indicating that both components of the chimera are required for virolysis. The finding that engaging the Env protein spike and membrane using a chimeric ligand can destabilize the virus and lead to inactivation opens up a means to investigate virus particle metastability and to evaluate this approach for inactivation at the earliest stages of exposure to virus and before host cell encounter.
Metrics
Details
- Title
- Chimeric Cyanovirin-MPER Recombinantly Engineered Proteins Cause Cell-Free Virolysis of HIV-1
- Creators
- Mark Contarino - Drexel University College of Medicine, Department of Biochemistry and Molecular Biology, Philadelphia, Pennsylvania, USAArangassery R Bastian - Drexel University College of Medicine, Department of Biochemistry and Molecular Biology, Philadelphia, Pennsylvania, USARamalingam Venkat Kalyana Sundaram - Drexel University College of Medicine, Department of Biochemistry and Molecular Biology, Philadelphia, Pennsylvania, USAKaryn McFadden - Duke University, Department of Molecular Genetics and Microbiology, Durham, North Carolina, USACaitlin Duffy - Drexel University College of Medicine, Department of Biochemistry and Molecular Biology, Philadelphia, Pennsylvania, USAVamshi Gangupomu - Drexel University, Department of Chemical and Biological Engineering, Philadelphia, Pennsylvania, USAMichelle Baker - Drexel University, Department of Chemical and Biological Engineering, Philadelphia, Pennsylvania, USACameron Abrams - Drexel University College of Medicine, Department of Biochemistry and Molecular Biology, Philadelphia, Pennsylvania, USAIrwin Chaiken - Drexel University College of Medicine, Department of Biochemistry and Molecular Biology, Philadelphia, Pennsylvania, USA
- Publication Details
- Antimicrobial agents and chemotherapy, v 57(10), pp 4743-4750
- Publisher
- American Society for Microbiology; 1752 N St., N.W., Washington, DC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Thomas R. Kline School of Law; Chemical and Biological Engineering
- Web of Science ID
- WOS:000324480300019
- Scopus ID
- 2-s2.0-84884261781
- Other Identifier
- 991014877714704721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy