dc.creator | Simeon, Rudo L. | |
dc.creator | Chen, Zhilei | |
dc.date.accessioned | 2014-02-27T22:09:02Z | |
dc.date.available | 2014-02-27T22:09:02Z | |
dc.date.issued | 2013-12-31 | |
dc.identifier.citation | Simeon RL, Chen Z (2013) A Screen for Genetic Suppressor Elements of Hepatitis C Virus Identifies a Supercharged Protein Inhibitor of Viral Replication. PLoS ONE 8(12): e84022. doi:10.1371/journal.pone.0084022 | en |
dc.identifier.uri | http://dx.doi.org/10.1371/journal.pone.0084022 | |
dc.identifier.uri | https://hdl.handle.net/1969.1/151491 | |
dc.description.abstract | Genetic suppressor elements (GSEs) are biomolecules derived from a gene or genome of interest that act as transdominant
inhibitors of biological functions presumably by disruption of critical biological interfaces. We exploited a cell death reporter
cell line for hepatitis C virus (HCV) infection, n4mBid, to develop an iterative selection/enrichment strategy for the
identification of anti-HCV GSEs. Using this approach, a library of fragments of an HCV genome was screened for sequences
that suppress HCV infection. A 244 amino acid gene fragment, B1, was strongly enriched after 5 rounds of selection. B1
derives from a single-base frameshift of the enhanced green fluorescent protein (eGFP) which was used as a filler during
fragment cloning. B1 has a very high net positive charge of 43 at neutral pH and a high charge-to-mass (kDa) ratio of 1.5. We
show that B1 expression specifically inhibits HCV replication. In addition, five highly positively charged B1 fragments
produced from progressive truncation at the C-terminus all retain the ability to inhibit HCV, suggesting that a high positive
charge, rather than a particular motif in B1, likely accounts for B1’s anti-HCV activity. Another supercharged protein,
+
36GFP,
was also found to strongly inhibit HCV replication when added to cells at the time of infection. This study reports a new
methodology for HCV inhibitor screening and points to the anti-HCV potential of positively charged proteins/peptides. | en |
dc.description.sponsorship | The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund. | en |
dc.language.iso | en_US | |
dc.publisher | PLoS | |
dc.rights | Attribution 3.0 United States | en |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | |
dc.title | A screen for genetic suppressor elements of hepatitis C virus identifies a supercharged protein inhibitor of viral replication | en |
dc.type | Article | en |
local.department | Chemical Engineering | en |
dc.rights.requestable | false | en |