Translation efficiency determines differences in cellular infection among dengue virus type 2 strains

We have investigated the molecular basis for differences in the ability of natural variants of dengue virus type 2 (DEN2) to replicate in primary human cells. The rates of virus binding, virus entry, input strand translation, and RNA stability of low-passage Thai and Nicaraguan and prototype DEN2 st...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2003-12, Vol.317 (2), p.275-290
Main Authors: Edgil, Dianna, Diamond, Michael S, Holden, Katherine L, Paranjape, Suman M, Harris, Eva
Format: Article
Language:English
Subjects:
3' Untranslated Regions - genetics
3′ Untranslated region
Animals
Cell Line
Cells, Cultured
Cricetinae
Dengue virus
Dengue Virus - classification
Dengue Virus - genetics
Dengue Virus - pathogenicity
Dengue Virus - physiology
Dengue virus type 2
Fibroblasts - virology
Flavivirus
Genetic Variation
Humans
Low-passage strains
Protein Biosynthesis
RNA, Viral - genetics
RNA, Viral - metabolism
Sequence Alignment
Sequence Analysis, DNA
Serial Passage
Translation
Virus Replication
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Summary:We have investigated the molecular basis for differences in the ability of natural variants of dengue virus type 2 (DEN2) to replicate in primary human cells. The rates of virus binding, virus entry, input strand translation, and RNA stability of low-passage Thai and Nicaraguan and prototype DEN2 strains were compared. All strains exhibited equivalent binding, entry, and uncoating, and displayed comparable stability of positive strand viral RNA over time in primary cells. However, the low-passage Nicaraguan isolates were much less efficient in their ability to translate viral proteins. Sequence analysis of the full-length low-passage Nicaraguan and Thai viral genomes identified specific differences in the 3′ untranslated region (3′UTR). Substitution of the different sequences into chimeric RNA reporter constructs demonstrated that the changes in the 3′UTR directly affected the efficiency of viral translation. Thus, differences in infectivity among closely related DEN2 strains correlate with efficiency of translation of input viral RNA.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2003.08.012