| dc.creator |
Gómez, Carmen E. |
|
| dc.creator |
Vandermeeren, Andrée M. |
|
| dc.creator |
García López, María Ángeles |
|
| dc.creator |
Domingo-Gil, Elena |
|
| dc.creator |
Esteban, Mariano |
|
| dc.date |
2008-04-08T09:23:19Z |
|
| dc.date |
2008-04-08T09:23:19Z |
|
| dc.date |
2005-09-12 |
|
| dc.date.accessioned |
2017-01-31T01:01:36Z |
|
| dc.date.available |
2017-01-31T01:01:36Z |
|
| dc.identifier |
Virol J. 2005; 2: 81 |
|
| dc.identifier |
1743-422X |
|
| dc.identifier |
http://hdl.handle.net/10261/3465 |
|
| dc.identifier |
10.1186/1743-422X-2-81 |
|
| dc.identifier.uri |
http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3465 |
|
| dc.description |
This article is available from: http://www.virologyj.com/content/2/1/81 |
|
| dc.description |
[Background] Hepatitis C virus (HCV) infection is of growing concern in public health with around
350 million chronically infected individuals worldwide. Although the IFN-α/rivabirin is the only
approved therapy with 10–30% clinical efficacy, the protective molecular mechanism involved
during the treatment is still unknown. To analyze the effect of HCV polyprotein expression on the
antiviral response of the host, we developed a novel vaccinia virus (VV)-based delivery system
(VT7-HCV7.9) where structural and nonstructural (except part of NS5B) proteins of HCV ORF
from genotype 1b are efficiently expressed and produced, and timely regulated in mammalian cell
lines. |
|
| dc.description |
[Results] Regulated transcript production and viral polypeptide processing was demonstrated in
various cell lines infected with the recombinant VT7-HCV7.9, indicating that the cellular and viral
proteolytic machineries are functional within these cells. The inducible expression of the HCV
polyprotein by VV inhibits the synthesis of both host and viral proteins over the time and also
induces apoptosis in HeLa and HepG2-infected cells. These effects occur accompanying with the
phosphorylation of the translation initiation factor eIF-2α. In cells co-infected with VT7-HCV7.9
and a recombinant VV expressing the dominant negative eIF-2α-S51A mutant in the presence of
the inductor isopropyl-thiogalactoside (IPTG), protein synthesis is rescued. The IFN-inducible
protein kinase PKR is responsible for the translational block, as demonstrated with PKR-/- and
PKR+/+ cell lines. However, apoptosis induced by VT7-HCV7.9 is mediated by the RNase L
pathway, in a PKR-independent manner. |
|
| dc.description |
[Conclusion] These findings demonstrate the antiviral relevance of the proteins induced by
interferon, PKR and RNase L during expression from a VV recombinant of the HCV polyprotein in
human cell lines. HCV polyprotein expression caused a severe cytopathological effect in human
cells as a result of inhibition of protein synthesis and apoptosis induction, triggered by the activation
of the IFN-induced enzymes PKR and RNase L systems. Thus, the virus-cell system described here
highlights the relevance of the IFN system as a protective mechanism against HCV infection. |
|
| dc.description |
This investigation was supported by research grants BIO2000-0340-P4,
BMC2002-03246 and Fundación Marcelino Botin from Spain and
QLK22002-00954 from the European Union to ME. CEG was supported by
a fellowship from Carolina Foundation and MAG from the Ministry of Science
and Technology of Spain. |
|
| dc.description |
Peer reviewed |
|
| dc.format |
1331866 bytes |
|
| dc.format |
application/pdf |
|
| dc.language |
eng |
|
| dc.publisher |
BioMed Central |
|
| dc.relation |
Publisher’s version |
|
| dc.rights |
openAccess |
|
| dc.title |
Involvement of PKR and RNase L in translational control and induction of apoptosis after Hepatitis C polyprotein expression from a Vaccinia virus recombinant |
|
| dc.type |
Artículo |
|