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Hepatitis C virus: The role of N-glycosylation sites of viral genotype 1b proteins for formation of viral particles in insect and mammalian cells

Hepatitis C virus (HCV) is characterized by considerable genetic variability and, as a consequence, it has 6 genotypes and multitude of subtypes. HCV envelope glycoproteins are involved in the virion formation; the correct folding of these proteins plays the key role in virus infectivity. Glycosylat...

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Autores principales: Beljelarskaya, S.N., Orlova, O.V., Drutsa, V.L., Orlov, V.A., Timohova, A.V., Koroleva, N.N., Popenko, V.I., Ivanov, A.V., Spirin, P.V., Prassolov, V.S., Rubtsov, P.M., Kochetkov, S.N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613296/
https://www.ncbi.nlm.nih.gov/pubmed/28955895
http://dx.doi.org/10.1016/j.bbrep.2016.05.019
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author Beljelarskaya, S.N.
Orlova, O.V.
Drutsa, V.L.
Orlov, V.A.
Timohova, A.V.
Koroleva, N.N.
Popenko, V.I.
Ivanov, A.V.
Spirin, P.V.
Prassolov, V.S.
Rubtsov, P.M.
Kochetkov, S.N.
author_facet Beljelarskaya, S.N.
Orlova, O.V.
Drutsa, V.L.
Orlov, V.A.
Timohova, A.V.
Koroleva, N.N.
Popenko, V.I.
Ivanov, A.V.
Spirin, P.V.
Prassolov, V.S.
Rubtsov, P.M.
Kochetkov, S.N.
author_sort Beljelarskaya, S.N.
collection PubMed
description Hepatitis C virus (HCV) is characterized by considerable genetic variability and, as a consequence, it has 6 genotypes and multitude of subtypes. HCV envelope glycoproteins are involved in the virion formation; the correct folding of these proteins plays the key role in virus infectivity. Glycosylation at certain sites of different genotypes HCV glycoproteins shows substantial differences in functions of the individual glycans (Goffard et al., 2005; Helle et al., 2010) [1], [2]. In this study, differential glycosylation sites of HCV genotype 1b envelope proteins in insect and mammalian cells was demonstrated. We showed that part of glycosylation sites was important for folding of the proteins involved in the formation of viral particles. Point mutations were introduced in the protein N-glycosylation sites of HCV (genotype 1b) and the mutant proteins were analyzed using baculovirus expression system in mammalian and insect cells. Our data showed that, in contrast to HCV 1a and 2a, the folding of HCV 1b envelope proteins E2 (sites N1, N2, N10) and E1 (sites N1, N5) was disrupted, however that did not prevent the formation of virus-like particles (VLP) with misfolded glycoproteins having densities typical for HCV particles containing RNA fragments. Experimental data are supported by mathematical modeling of the structure of E1 mutant variants.
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spelling pubmed-56132962017-09-27 Hepatitis C virus: The role of N-glycosylation sites of viral genotype 1b proteins for formation of viral particles in insect and mammalian cells Beljelarskaya, S.N. Orlova, O.V. Drutsa, V.L. Orlov, V.A. Timohova, A.V. Koroleva, N.N. Popenko, V.I. Ivanov, A.V. Spirin, P.V. Prassolov, V.S. Rubtsov, P.M. Kochetkov, S.N. Biochem Biophys Rep Research Article Hepatitis C virus (HCV) is characterized by considerable genetic variability and, as a consequence, it has 6 genotypes and multitude of subtypes. HCV envelope glycoproteins are involved in the virion formation; the correct folding of these proteins plays the key role in virus infectivity. Glycosylation at certain sites of different genotypes HCV glycoproteins shows substantial differences in functions of the individual glycans (Goffard et al., 2005; Helle et al., 2010) [1], [2]. In this study, differential glycosylation sites of HCV genotype 1b envelope proteins in insect and mammalian cells was demonstrated. We showed that part of glycosylation sites was important for folding of the proteins involved in the formation of viral particles. Point mutations were introduced in the protein N-glycosylation sites of HCV (genotype 1b) and the mutant proteins were analyzed using baculovirus expression system in mammalian and insect cells. Our data showed that, in contrast to HCV 1a and 2a, the folding of HCV 1b envelope proteins E2 (sites N1, N2, N10) and E1 (sites N1, N5) was disrupted, however that did not prevent the formation of virus-like particles (VLP) with misfolded glycoproteins having densities typical for HCV particles containing RNA fragments. Experimental data are supported by mathematical modeling of the structure of E1 mutant variants. Elsevier 2016-05-30 /pmc/articles/PMC5613296/ /pubmed/28955895 http://dx.doi.org/10.1016/j.bbrep.2016.05.019 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Beljelarskaya, S.N.
Orlova, O.V.
Drutsa, V.L.
Orlov, V.A.
Timohova, A.V.
Koroleva, N.N.
Popenko, V.I.
Ivanov, A.V.
Spirin, P.V.
Prassolov, V.S.
Rubtsov, P.M.
Kochetkov, S.N.
Hepatitis C virus: The role of N-glycosylation sites of viral genotype 1b proteins for formation of viral particles in insect and mammalian cells
title Hepatitis C virus: The role of N-glycosylation sites of viral genotype 1b proteins for formation of viral particles in insect and mammalian cells
title_full Hepatitis C virus: The role of N-glycosylation sites of viral genotype 1b proteins for formation of viral particles in insect and mammalian cells
title_fullStr Hepatitis C virus: The role of N-glycosylation sites of viral genotype 1b proteins for formation of viral particles in insect and mammalian cells
title_full_unstemmed Hepatitis C virus: The role of N-glycosylation sites of viral genotype 1b proteins for formation of viral particles in insect and mammalian cells
title_short Hepatitis C virus: The role of N-glycosylation sites of viral genotype 1b proteins for formation of viral particles in insect and mammalian cells
title_sort hepatitis c virus: the role of n-glycosylation sites of viral genotype 1b proteins for formation of viral particles in insect and mammalian cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613296/
https://www.ncbi.nlm.nih.gov/pubmed/28955895
http://dx.doi.org/10.1016/j.bbrep.2016.05.019
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