Cross-reactive pseudovirus-neutralizing anti-envelope antibodies coexist with antibodies devoid of such activity in persistent hepatitis C virus infection.
Most RNA viruses have evolved mechanisms to avoid neutralizing antibody responses, and it is generally believed that variability of envelope-encoding regions is the major molecular basis of this phenomenon. However, it has been hypothesized that other mechanisms can be involved. Recent experimental data indicate that in hepatitis C virus (HCV) infection, the anti-envelope humoral response includes cross-reactive antibody clones able to neutralize vesicular stomatitis virus (VSV) pseudotypes containing HCV E1 and E2 glycoproteins (HCV/VSV pseudotype) as well as other clones devoid of such activity. In this work, we demonstrate that natural infection with a large variety of HCV isolates belonging to different genotypes elicits HCV/VSV pseudotype-neutralizing cross-reactive anti-envelope antibodies together with clones unable to neutralize this pseudovirus. This was shown by designing a novel strategy for quantitation of serum antibodies binding selectively to single viral cross-reactive conformational epitopes. These data can be useful not only for a better understanding of the virus-host interplay in important viral diseases, but also for the development of an effective anti-HCV vaccine.
Burioni
Roberto
R
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università di Ancona, 60020 Ancona, Italy. robertoburioni@yahoo.com
Mancini
Nicasio
N
Carletti
Silvia
S
Perotti
Mario
M
Grieco
Antonella
A
Canducci
Filippo
F
Varaldo
Pietro E
PE
Clementi
Massimo
M
D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D003429:Cross Reactions; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; C087035:E1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D007140:Immunoglobulin Fab Fragments; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus