Abstract
Membrane fusion is an essential step in the entry of enveloped viruses into their host cells, what makes it a potentially attractive target for viral inactivation approaches. Fusion is mediated by viral surface glycoproteins that undergo conformational changes triggered by interaction with specific cellular receptors or by the exposition to low pH of endossomal medium. Here we review how several studies on the structural rearrangements of vesicular stomatitis virus (VSV) glycoprotein G during cellular recognition and fusion led us to propose a crucial role of the protonation of His residues for G protein activity. Moreover, we demonstrated that using diethylpyrocarbonate (DEPC), a histidine-modifying compound, it was possible to abolish viral infectivity and pathogenicity in mice, and to elicit neutralizing antibodies that confer protection in these animals against challenge using lethal doses of the virus. The presence of conserved His residues in a wide range of viral fusion proteins and the use of DEPC as a more general means for vaccine development will be also discussed.
Keywords: Membrane fusion, viral inactivation, histidine protonation, vesicular stomatitis virus, diethylpyrocarbonate
Protein & Peptide Letters
Title: Viral Inactivation Based on Inhibition of Membrane Fusion: Understanding the Role of Histidine Protonation to Develop New Viral Vaccines
Volume: 16 Issue: 7
Author(s): A.T. Da Poian, F. A. Carneiro and F. Stauffer
Affiliation:
Keywords: Membrane fusion, viral inactivation, histidine protonation, vesicular stomatitis virus, diethylpyrocarbonate
Abstract: Membrane fusion is an essential step in the entry of enveloped viruses into their host cells, what makes it a potentially attractive target for viral inactivation approaches. Fusion is mediated by viral surface glycoproteins that undergo conformational changes triggered by interaction with specific cellular receptors or by the exposition to low pH of endossomal medium. Here we review how several studies on the structural rearrangements of vesicular stomatitis virus (VSV) glycoprotein G during cellular recognition and fusion led us to propose a crucial role of the protonation of His residues for G protein activity. Moreover, we demonstrated that using diethylpyrocarbonate (DEPC), a histidine-modifying compound, it was possible to abolish viral infectivity and pathogenicity in mice, and to elicit neutralizing antibodies that confer protection in these animals against challenge using lethal doses of the virus. The presence of conserved His residues in a wide range of viral fusion proteins and the use of DEPC as a more general means for vaccine development will be also discussed.
Export Options
About this article
Cite this article as:
Da Poian A.T., Carneiro A. F. and Stauffer F., Viral Inactivation Based on Inhibition of Membrane Fusion: Understanding the Role of Histidine Protonation to Develop New Viral Vaccines, Protein & Peptide Letters 2009; 16 (7) . https://dx.doi.org/10.2174/092986609788681823
DOI https://dx.doi.org/10.2174/092986609788681823 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Drug Targets from Human Pathogenic Amoebas: Entamoeba histolytica,Acanthamoeba polyphaga and Naegleria fowleri
Infectious Disorders - Drug Targets Etiology of Neuroinflammatory Pathologies in Neurodegenerative Diseases: A Treatise
Current Psychopharmacology Discovery, SAR and Medicinal Chemistry of Herpesvirus Helicase Primase Inhibitors
Current Medicinal Chemistry - Anti-Infective Agents Viral Myocarditis and Dilated Cardiomyopathy: Etiology and Pathogenesis
Current Pharmaceutical Design Innate Immunity and Intracellular Trafficking: Insights for Novel Anti- HIV-1 Therapeutics
Current Pharmacogenomics BACE1 Levels Correlate with Phospho-Tau Levels in Human Cerebrospinal Fluid
Current Alzheimer Research Glycoconjugates: Roles in Neural Diseases Caused by Exogenous Pathogens
CNS & Neurological Disorders - Drug Targets Developments in High-Yield System Expressed Vaccines and Immunotherapy
Recent Patents on Biotechnology Mitochondrial Dysfunction in Huntington’s Disease: Pathogenesis and Therapeutic Opportunities
Current Drug Targets The 5-lipoxygenase (5-LOX) Inhibitor Zileuton Reduces Inflammation and Infarct Size with Improvement in Neurological Outcome Following Cerebral Ischemia
Current Neurovascular Research Hendra and Nipah Viruses: Pathogenesis and Therapeutics
Current Molecular Medicine Disorders of Consciousness and Pharmaceuticals that Act on Oxygen Based Amino Acid and Monoamine Neurotransmitter Pathways of the Brain
Current Pharmaceutical Design Editorial: “Phytochemicals for Human Diseases: An Update”
Current Drug Targets Role of Cytokines in Neurological Disorders
Current Medicinal Chemistry What Animal Models are Best to Test Novel Rheumatoid Arthritis Therapies?
Current Rheumatology Reviews Inflammation and Age-Related Iron Accumulation in F344 Rats
Current Aging Science Immunological Mechanisms of Neuropsychiatric Lupus
Current Immunology Reviews (Discontinued) Inhibition of RNA Virus Infections with Peptide-Conjugated Morpholino Oligomers
Current Pharmaceutical Design Recent Advances in the Imaging of Programmed Cell Death
Current Pharmaceutical Design Is Helicobacter pylori the Infectious Trigger for Headache?: A Review
Infectious Disorders - Drug Targets