July 9, 2013

Structural and Antigenic Definition of Hepatitis C Virus E2 Glycoprotein Epitopes Targeted by Monoclonal Antibodies


Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 450963, 12 pages
http://dx.doi.org/10.1155/2013/450963
Review Article

Structural and Antigenic Definition of Hepatitis C Virus E2 Glycoprotein Epitopes Targeted by Monoclonal Antibodies

1Laboratorio di Microbiologia e Virologia, Università Vita-Salute San Raffaele, Via Olgettina 58, 20132 Milano, Italy
2School of Molecular Medical Sciences, The University of Nottingham, Nottingham NG7 2UH, UK
3Biomedical Research Unit in Gastrointestinal and Liver Diseases, The University of Nottingham, Nottingham NG7 2UH, UK
Received 9 May 2013; Accepted 10 June 2013
Academic Editor: Roberto Burioni
Copyright © 2013 Giuseppe Sautto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Hepatitis C virus (HCV) is the major cause of chronic liver disease as well as the major indication for liver transplantation worldwide. Current standard of care is not completely effective, not administrable in grafted patients, and burdened by several side effects. This incomplete effectiveness is mainly due to the high propensity of the virus to continually mutate under the selective pressure exerted by the host immune response as well as currently administered antiviral drugs. The E2 envelope surface glycoprotein of HCV (HCV/E2) is the main target of the host humoral immune response and for this reason one of the major variable viral proteins. However, broadly cross-neutralizing monoclonal antibodies (mAbs) directed against HCV/E2 represent a promising tool for the study of virus-host interplay as well as for the development of effective prophylactic and therapeutic approaches. In the last few years many anti-HCV/E2 mAbs have been evaluated in preclinical and clinical trials as possible candidate antivirals, particularly for administration in pre- and post-transplant settings. In this review we summarize the antigenic and structural characteristics of HCV/E2 determined through the use of anti-HCV/E2 mAbs, which, given the absence of a crystal structure of this glycoprotein, represent currently the best tool available.

No comments:

Post a Comment