Inactivation of vesicular stomatitis virus through inhibition of membrane fusion by chemical modification of the viral glycoprotein.
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 0.5mM 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.
Stauffer
Fausto
F
Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-590, Brazil.
De Miranda
Joari
J
Schechter
Marcos C
MC
Carneiro
Fabiana A
FA
Salgado
Leonardo T
LT
Machado
Gisele F
GF
Da Poian
Andrea T
AT
D000818:Animals; D006224:Cricetinae; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000187:drug effects*; D038301:Virus Inactivation / Q000187:drug effects*
C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D004047:Diethyl Pyrocarbonate