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Translation efficiency determines differences in cellular infection among dengue virus type 2 strains
Dianna Edgil1, Michael S Diamond, Katherine L Holden
1Division of Infectious Diseases, School of Public Health, University of California, Berkeley, CA 94720-7360, USA.
Virology
|December 31, 2003
Summary
Differences in dengue virus type 2 (DEN2) infectivity stem from variations in viral protein translation efficiency. Specific genetic changes in the 3' untranslated region (3'UTR) directly impact this translation process, affecting DEN2 replication in human cells.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Natural variants of dengue virus type 2 (DEN2) exhibit differing replication capabilities in human cells.
- Understanding the molecular basis of these differences is crucial for controlling DEN2 infections.
Purpose of the Study:
- To investigate the molecular mechanisms underlying replication differences among natural DEN2 variants.
- To identify specific viral genetic elements responsible for variations in DEN2 infectivity.
Main Methods:
- Comparative analysis of virus binding, entry, translation, and RNA stability for Thai and Nicaraguan DEN2 strains.
- Full-length genome sequencing of low-passage DEN2 isolates.
- Functional characterization of the 3' untranslated region (3'UTR) using RNA reporter constructs.
Main Results:
- All DEN2 strains showed comparable binding, entry, uncoating, and RNA stability.
- Nicaraguan DEN2 isolates demonstrated significantly lower efficiency in viral protein translation.
- Sequence analysis revealed distinct differences in the 3'UTR between Thai and Nicaraguan strains.
- Altering 3'UTR sequences in reporter constructs directly impacted viral translation efficiency.
Conclusions:
- Infectivity variations among closely related DEN2 strains correlate with the efficiency of input viral RNA translation.
- The 3'UTR is a key determinant of translational efficiency and, consequently, DEN2 infectivity.