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 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.
Edgil
Dianna
D
Division of Infectious Diseases, School of Public Health, University of California, Berkeley, CA 94720-7360, USA.
Diamond
Michael S
MS
Holden
Katherine L
KL
Paranjape
Suman M
SM
Harris
Eva
E
D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D003716:Dengue Virus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D005347:Fibroblasts / Q000821:virology; D014644:Genetic Variation; D006801:Humans; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D014779:Virus Replication
D020413:3' Untranslated Regions; D012367:RNA, Viral