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.
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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 |
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