Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/66498
Title: Interplay between Basic Residues of Hepatitis C Virus Glycoprotein E2 with Vi ral Receptors Neutralizing Antibodies and Lipoproteins.
Author: Koutsoudakis, G.
Dragun, J.
Pérez del Pulgar, S.
Coto-Llerena, M.
Mensa, K.
Crespo Conde, Gonzalo
González, P.
Navasa, Miquel
Forns, Xavier
Keywords: Hepatitis C
Glicoproteïnes
Genètica molecular
Hepatitis C
Glycoproteins
Molecular genetics
Issue Date: 27-Dec-2012
Publisher: Public Library of Science (PLoS)
Abstract: Positively-charged amino acids are located at specific positions in the envelope glycoprotein E2 of the hepatitis C virus (HCV): two histidines (H) and four arginines (R) in two conserved WHY and one RGERCDLEDRDR motifs, respectively. Additionally, the E2 hypervariable region 1 (HVR1) is rich in basic amino acids. To investigate the role(s) of these residues in HCV entry, we subjected to comparative infection and sedimentation analysis cell culture-produced (HCVcc, genotype 2a) wild type virus, a panel of alanine single-site mutants and a HVR1-deletion variant. Initially, we analyzed the effects of these mutations on E2-heparan sulfate (HS) interactions. The positive milieu of the HVR1, formulated by its basic amino acids (key residues the conserved H386 and R408), and the two highly conserved basic residues H488 and R648 contributed to E2-HS interactions. Mutations in these residues did not alter the HCVcc-CD81 entry, but they modified the HCVcc-scavenger receptor class B type I (SR-BI) dependent entry and the neutralization by anti-E2 or patients IgG. Finally, separation by density gradients revealed that mutant viruses abolished partially or completely the infectivity of low density particles, which are believed to be associated with lipoproteins. This study shows that there exists a complex interplay between the basic amino acids located in HVR1 and other conserved E2 motifs with the HS, the SR-BI, and neutralizing antibodies and suggests that HCV-associated lipoproteins are implicated in these interactions.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0052651
It is part of: PLoS One, 2012, vol. 7, num. 12, p. e52651
Related resource: http://dx.doi.org/10.1371/journal.pone.0052651
URI: http://hdl.handle.net/2445/66498
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Medicina)

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