Inactivation of vesicular stomatitis virus through inhibition of membrane fusion by chemical modification of the viral glycoprotein
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Elsevier
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Membrane fusion is an essential step in the entry of enveloped viruses into their host cells triggered by conformational changes in viral glycoproteins. We have demonstrated previously that modification of vesicular stomatitis virus (VSV) with diethylpyrocarbonate (DEPC) abolished conformational changes on VSV glycoprotein and the fusion reaction catalyzed by the virus. In the present study, we evaluated whether treatment with DEPC was able to inactivate the virus. Infectivity and viral replication were abolished by viral treatment with 0.5 mM DEPC. Mortality profile and inflammatory response in the central nervous system indicated that G protein modification with DEPC eliminates the ability of the virus to cause disease. In addition, DEPC treatment did not alter the conformational integrity of surface proteins of inactivated VSV as demonstrated by transmission electron microscopy and competitive ELISA. Taken together, our results suggest a potential use of histidine (His) modification to the development of a new process of viral inactivation based on fusion inhibition. © 2006 Elsevier B.V. All rights reserved.
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Diethylpyrocarbonate , Membrane fusion , Vesicular stomatitis virus , Viral inactivation , diethyl pyrocarbonate , histidine , hydroxylamine , virus glycoprotein , animal cell , animal experiment , animal model , animal tissue , brain infection , chemical modification , conformational transition , controlled study , drug dose comparison , enzyme linked immunosorbent assay , male , membrane fusion , mouse , nonhuman , priority journal , protein conformation , RNA virus infection , transmission electron microscopy , virus cell interaction , virus inactivation , virus infectivity , virus replication , virus titration , Animals , Cricetinae , Diethyl Pyrocarbonate , Disease Models, Animal , Humans , Membrane Fusion , Membrane Glycoproteins , Mice , Mice, Inbred BALB C , Vesicular stomatitis-Indiana virus , Viral Envelope Proteins , Virus Inactivation
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Antiviral Research, v. 73, n. 1, p. 31-39, 2007.
