TY - JOUR
T1 - Translation efficiency determines differences in cellular infection among dengue virus type 2 strains
AU - Edgil, Dianna
AU - Diamond, Michael S.
AU - Holden, Katherine L.
AU - Paranjape, Suman M.
AU - Harris, Eva
N1 - Funding Information:
We are grateful to Rebeca Rico-Hesse for low-passage Thai strains and to Andrea Gamarnik and Josefina Coloma for helpful discussions. We thank Karen Clyde for assistance with computer prediction of secondary structure and Loy Volkman, Robert Beatty, Anna-Marija Helt, José Peña, and Sujan Shresta for editorial comments. This work was supported by the Pew Charitable Trusts (#2617SC) and the Committee on Research at the University of California, Berkeley.
PY - 2003/12/20
Y1 - 2003/12/20
N2 - 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.
AB - 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.
KW - 3′ Untranslated region
KW - Dengue virus
KW - Flavivirus
KW - Low-passage strains
KW - Translation
UR - http://www.scopus.com/inward/record.url?scp=0347416791&partnerID=8YFLogxK
U2 - 10.1016/j.virol.2003.08.012
DO - 10.1016/j.virol.2003.08.012
M3 - Article
C2 - 14698666
AN - SCOPUS:0347416791
SN - 0042-6822
VL - 317
SP - 275
EP - 290
JO - Virology
JF - Virology
IS - 2
ER -