Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-5-21
pubmed:abstractText
Hepatitis C virus (HCV) is a human RNA virus encoding 10 proteins in a single open reading frame. In the +1 frame, an 'alternate reading frame' (ARF) overlaps with the core protein-encoding sequence and encodes the ARF protein (ARFP). Here, we investigated the molecular regulatory mechanisms of ARFP expression in HCV target cells. Chimeric HCV-luciferase reporter constructs derived from the infectious HCV prototype isolate H77 were transfected into hepatocyte-derived cell lines. Translation initiation was most efficient at the internal AUG codon at position 86/88, resulting in the synthesis of a truncated ARFP named (86/88)ARFP. Interestingly, (86/88)ARFP synthesis was markedly enhanced in constructs containing an inactivated core protein reading frame. This enhancement was reversed by co-expression of core protein in trans, demonstrating suppression of ARFP synthesis by HCV core protein. In conclusion, our results indicate that translation of ARFP occurs mainly by alternative internal initiation at position 86/88 and is regulated by HCV core protein expression. The suppression of ARFP translation by HCV core protein suggests that ARFP expression is inversely linked to the level of viral replication. These findings define key mechanisms regulating ARFP expression and set the stage for further studies addressing the function of ARFP within the viral life cycle.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-10051634, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-10075915, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-10559281, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-10644379, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-10764589, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-10895428, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-11070035, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-11350035, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-11447125, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-11853407, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-11884417, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-11943474, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-12368308, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-12502871, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-12519954, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-12655082, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-12692242, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-12702818, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-12771425, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-12810869, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-12874283, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-1310188, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-1310756, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-15147837, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-15367612, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-15382175, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-15702954, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-15755749, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-16510853, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-16971433, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-17059566, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-17110442, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-17299041, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-17631420, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-2033677, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-2164889, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-2170120, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-2214021, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-2999308, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-3889910, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-8189501, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-8267715, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-8676512, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-9228008, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400784-9238047
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1362-4962
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3054-64
pubmed:dateRevised
2010-9-22
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
The major form of hepatitis C virus alternate reading frame protein is suppressed by core protein expression.
pubmed:affiliation
Inserm, U748, Université Louis Pasteur, Strasbourg and Service d'Hépatogastroentérologie, Hôpitaux Universitaires de Strasbourg, F-67000, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't