Comparative analysis of translation efficiencies of hepatitis C virus 5' untranslated regions among intraindividual quasispecies present in chronic infection: opposite behaviors depending on cell type.
Hepatitis C virus (HCV) RNA translation initiation is dependent on the presence of an internal ribosome entry site (IRES) that is found mostly in its 5' untranslated region (5' UTR). While exhibiting the most highly conserved sequence within the genome, the 5' UTR accumulates small differences, which may be of biological and clinical importance. In this study, using a bicistronic dual luciferase expression system, we have examined the sequence of 5' UTRs from quasispecies characterized in the serum of a patient chronically infected with HCV genotype 1a and its corresponding translational activity. Sequence heterogeneity between IRES elements led to important changes in their translation efficiency both in vitro and in different cell cultures lines, implying that interactions of RNA with related transacting factors may vary according to cell type. These data suggest that variants occasionally carried by the serum prior to reinfection could be selected toward different compartments of the same infected organism, thus favoring the hypothesis of HCV multiple tropism.
Laporte
J
J
Laboratoire de virologie, C.E.R.V.I., UPRES EA 2387, Hôpital Pitié-Salpêtrière, 75651 Paris Cedex 13, France.
Malet
I
I
Andrieu
T
T
Thibault
V
V
Toulme
J J
JJ
Wychowski
C
C
Pawlotsky
J M
JM
Huraux
J M
JM
Agut
H
H
Cahour
A
A
D020121:5' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D005822:Genetic Vectors; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012270:Ribosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection
D020121:5' Untranslated Regions; D008156:Luciferases