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Abstract:

•Cholesterol in the virion envelope is essential for dengue virus infectivity.•The four dengue serotypes are similarly inactivated by cholesterol-extracting drugs.•Dengue virus uncoating is blocked in infection with cholesterol-depleted virions.•Virion treatment with exogenous cholesterol exert also a virucidal effect.•Cholesterol in the cell membranes is not required for dengue virus entry. The role of cholesterol in the virus envelope or in the cellular membranes for dengue virus (DENV) infection was examined by depletion with methyl-beta-cyclodextrin (MCD) or nystatin. Pretreatment of virions with MCD or nystatin significantly reduced virus infectivity in a dose-dependent manner. By contrast, pre-treatment of diverse human cell lines with MCD or nystatin did not affect DENV infection. The four DENV serotypes were similarly inactivated by cholesterol-extracting drugs and infectivity was partially rescued when virion suspensions were treated with MCD in the presence of bovine serum. The addition of serum or exogenous water-soluble cholesterol after MCD treatment did not produce a reversion of MCD inactivating effect. Furthermore, virion treatment with extra cholesterol exerted also a virucidal effect. Binding and uptake of cholesterol-deficient DENV into the host cell were not impaired, whereas the next step of fusion between virion envelope and endosome membrane leading to virion uncoating and release of nucleocapsids to the cytoplasm appeared to be prevented, as determined by the retention of capsid protein in cells infected with MCD inactivated-DENV virions. Thereafter, the infection was almost completely inhibited, given the failure of viral RNA synthesis and viral protein expression in cells infected with MCD-treated virions. These data suggest that envelope cholesterol is a critical factor in the fusion process for DENV entry. © 2013 Elsevier B.V.

Registro:

Documento: Artículo
Título:Requirement of cholesterol in the viral envelope for dengue virus infection
Autor:Carro, A.C.; Damonte, E.B.
Filiación:Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET, Ciudad Universitaria, Pabellón 2, Piso 4, 1428 Buenos Aires, Argentina
Palabras clave:Cholesterol; Dengue virus; Infectivity; Methyl-beta-cyclodextrin; Viral envelope; Virucidal activity; capsid protein; cholesterol; methyl beta cyclodextrin; nystatin; protein; virus protein; virus RNA; animal cell; article; cell membrane; controlled study; cytoplasm; dengue; endosome; host cell; human; human cell; nonhuman; priority journal; RNA synthesis; serotype; virion; virus attachment; virus envelope; virus expression; virus infectivity; virus nucleocapsid; Cell Line; Cholesterol; Dengue Virus; Humans; Membrane Lipids; Virus Internalization; Bovinae; Dengue virus; Miridae
Año:2013
Volumen:174
Número:1-2
Página de inicio:78
Página de fin:87
DOI: http://dx.doi.org/10.1016/j.virusres.2013.03.005
Título revista:Virus Research
Título revista abreviado:Virus Res.
ISSN:01681702
CODEN:VIRED
CAS:cholesterol, 57-88-5; nystatin, 1400-61-9, 34786-70-4, 62997-67-5; protein, 67254-75-5; Cholesterol, 57-88-5; Membrane Lipids; viral envelope lipids
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01681702_v174_n1-2_p78_Carro

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Citas:

---------- APA ----------
Carro, A.C. & Damonte, E.B. (2013) . Requirement of cholesterol in the viral envelope for dengue virus infection. Virus Research, 174(1-2), 78-87.
http://dx.doi.org/10.1016/j.virusres.2013.03.005
---------- CHICAGO ----------
Carro, A.C., Damonte, E.B. "Requirement of cholesterol in the viral envelope for dengue virus infection" . Virus Research 174, no. 1-2 (2013) : 78-87.
http://dx.doi.org/10.1016/j.virusres.2013.03.005
---------- MLA ----------
Carro, A.C., Damonte, E.B. "Requirement of cholesterol in the viral envelope for dengue virus infection" . Virus Research, vol. 174, no. 1-2, 2013, pp. 78-87.
http://dx.doi.org/10.1016/j.virusres.2013.03.005
---------- VANCOUVER ----------
Carro, A.C., Damonte, E.B. Requirement of cholesterol in the viral envelope for dengue virus infection. Virus Res. 2013;174(1-2):78-87.
http://dx.doi.org/10.1016/j.virusres.2013.03.005