Monoclonal antibodies against Hepatitis C genotype 3a virus like particle inhibit virus entry in cell culture system.

The envelope protein (E1-E2) of Hepatitis C virus (HCV) is a major component of the viral structure. The glycosylated envelope protein is considered to be important for initiation of infection by binding to cellular receptor(s) and also known as one of the major antigenic targets to host immune resp...

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Autores principales: Soma Das, Rohini K Shetty, Anuj Kumar, Radhika Nagamangalam Shridharan, Ranjitha Tatineni, Giriprakash Chi, Anirban Mukherjee, Saumitra Das, Shaila Melkote Subbarao, Anjali Anoop Karande
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:6853266eed7740dfafd7b342062554f12021-11-18T08:01:20ZMonoclonal antibodies against Hepatitis C genotype 3a virus like particle inhibit virus entry in cell culture system.1932-620310.1371/journal.pone.0053619https://doaj.org/article/6853266eed7740dfafd7b342062554f12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23341957/?tool=EBIhttps://doaj.org/toc/1932-6203The envelope protein (E1-E2) of Hepatitis C virus (HCV) is a major component of the viral structure. The glycosylated envelope protein is considered to be important for initiation of infection by binding to cellular receptor(s) and also known as one of the major antigenic targets to host immune response. The present study was aimed at identifying mouse monoclonal antibodies which inhibit binding of virus like particles of HCV to target cells. The first step in this direction was to generate recombinant HCV-like particles (HCV-LPs) specific for genotypes 3a of HCV (prevalent in India) using the genes encoding core, E1 and E2 envelop proteins in a baculovirus expression system. The purified HCV-LPs were characterized by ELISA and electron microscopy and were used to generate monoclonal antibodies (mAbs) in mice. Two monoclonal antibodies (E8G9 and H1H10) specific for the E2 region of envelope protein of HCV genotype 3a, were found to reduce the virus binding to Huh7 cells. However, the mAbs generated against HCV genotype 1b (D2H3, G2C7, E1B11) were not so effective. More importantly, mAb E8G9 showed significant inhibition of the virus entry in HCV JFH1 cell culture system. Finally, the epitopic regions on E2 protein which bind to the mAbs have also been identified. Results suggest a new therapeutic strategy and provide the proof of concept that mAb against HCV-LP could be effective in preventing virus entry into liver cells to block HCV replication.Soma DasRohini K ShettyAnuj KumarRadhika Nagamangalam ShridharanRanjitha TatineniGiriprakash ChiAnirban MukherjeeSaumitra DasShaila Melkote SubbaraoAnjali Anoop KarandePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53619 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Soma Das
Rohini K Shetty
Anuj Kumar
Radhika Nagamangalam Shridharan
Ranjitha Tatineni
Giriprakash Chi
Anirban Mukherjee
Saumitra Das
Shaila Melkote Subbarao
Anjali Anoop Karande
Monoclonal antibodies against Hepatitis C genotype 3a virus like particle inhibit virus entry in cell culture system.
description The envelope protein (E1-E2) of Hepatitis C virus (HCV) is a major component of the viral structure. The glycosylated envelope protein is considered to be important for initiation of infection by binding to cellular receptor(s) and also known as one of the major antigenic targets to host immune response. The present study was aimed at identifying mouse monoclonal antibodies which inhibit binding of virus like particles of HCV to target cells. The first step in this direction was to generate recombinant HCV-like particles (HCV-LPs) specific for genotypes 3a of HCV (prevalent in India) using the genes encoding core, E1 and E2 envelop proteins in a baculovirus expression system. The purified HCV-LPs were characterized by ELISA and electron microscopy and were used to generate monoclonal antibodies (mAbs) in mice. Two monoclonal antibodies (E8G9 and H1H10) specific for the E2 region of envelope protein of HCV genotype 3a, were found to reduce the virus binding to Huh7 cells. However, the mAbs generated against HCV genotype 1b (D2H3, G2C7, E1B11) were not so effective. More importantly, mAb E8G9 showed significant inhibition of the virus entry in HCV JFH1 cell culture system. Finally, the epitopic regions on E2 protein which bind to the mAbs have also been identified. Results suggest a new therapeutic strategy and provide the proof of concept that mAb against HCV-LP could be effective in preventing virus entry into liver cells to block HCV replication.
format article
author Soma Das
Rohini K Shetty
Anuj Kumar
Radhika Nagamangalam Shridharan
Ranjitha Tatineni
Giriprakash Chi
Anirban Mukherjee
Saumitra Das
Shaila Melkote Subbarao
Anjali Anoop Karande
author_facet Soma Das
Rohini K Shetty
Anuj Kumar
Radhika Nagamangalam Shridharan
Ranjitha Tatineni
Giriprakash Chi
Anirban Mukherjee
Saumitra Das
Shaila Melkote Subbarao
Anjali Anoop Karande
author_sort Soma Das
title Monoclonal antibodies against Hepatitis C genotype 3a virus like particle inhibit virus entry in cell culture system.
title_short Monoclonal antibodies against Hepatitis C genotype 3a virus like particle inhibit virus entry in cell culture system.
title_full Monoclonal antibodies against Hepatitis C genotype 3a virus like particle inhibit virus entry in cell culture system.
title_fullStr Monoclonal antibodies against Hepatitis C genotype 3a virus like particle inhibit virus entry in cell culture system.
title_full_unstemmed Monoclonal antibodies against Hepatitis C genotype 3a virus like particle inhibit virus entry in cell culture system.
title_sort monoclonal antibodies against hepatitis c genotype 3a virus like particle inhibit virus entry in cell culture system.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/6853266eed7740dfafd7b342062554f1
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