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. 2012 Feb 5;423(1):58-67.
doi: 10.1016/j.virol.2011.11.018. Epub 2011 Dec 16.

Genetic and phenotypic characterization of sylvatic dengue virus type 4 strains

S L Rossi  1 , F Nasar, J Cardosa, S V Mayer, R B Tesh, K A Hanley, S C Weaver, Nikos Vasilakis
Affiliations

Genetic and phenotypic characterization of sylvatic dengue virus type 4 strains

S L Rossi et al. Virology. .

Abstract

Four serotypes of dengue virus (DENV 1-4) currently circulate between humans and domestic/peridomestic Aedes mosquitoes, resulting in 100 million infections per year. All four serotypes emerged, independently, from sylvatic progenitors transmitted among non-human primates by arboreal Aedes mosquitoes. This study investigated the genetic and phenotypic changes associated with emergence of human DENV-4 from its sylvatic ancestors. Analysis of complete genomes of 3 sylvatic and 4 human strains revealed high conservation of both the 5'- and 3'-untranslated regions but considerable divergence within the open reading frame. Additionally, the two ecotypes did not differ significantly in replication dynamics in cultured human liver (Huh-7), monkey kidney (Vero) or mosquito (C6/36) cells, although significant inter-strain variation within ecotypes was detected. These findings are in partial agreement with previous studies of DENV-2, where human strains produced a larger number of progeny than sylvatic strains in human liver cells but not in monkey or mosquito cells.

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Figures

Figure 1
Figure 1. Phylogenetic analysis of sylvatic DENV-4 isolates
Phylogenetic tree derived from complete genome nucleotide sequences of sylvatic and human DENV-4 strains using Bayesian analysis. Numbers of posterior probability values for monophyletic groups to the right. Asterisks indicate DENV strains used to evaluate replication kinetics. Virus strains are coded by abbreviated country of collection/strain name/year of collection. The scale shows a genetic distance of 0.02 or 2% nucleotide sequence divergence
Figure 2
Figure 2. Comparative replication curves of DENV-4 strains
a–c: Daily virus output from days 0–6 following infection at MOI 0.01 by sylvatic (P73-1120, P75-215 and P75-514) and human (Haiti73, IndiaG11337, INH6412 and H241) DENV-4 strains in mosquito cell line C6/36 (Ae. albopictus) and vertebrate cell lines Vero (African green monkey kidney) and Huh-7 (human hepatoma) (a–c, respectively). d–f: Mean virus output of human (squares) and sylvatic (diamonds) DENV-4 strains in C6/36, Vero, and Huh-7 cells (d–f, respectively); means derived from 3 strains of sylvatic and four human DENV-4 shown in panels a–c. The limit of detection of the assay is 0.9 log10 ffu/mL.
Figure 2
Figure 2. Comparative replication curves of DENV-4 strains
a–c: Daily virus output from days 0–6 following infection at MOI 0.01 by sylvatic (P73-1120, P75-215 and P75-514) and human (Haiti73, IndiaG11337, INH6412 and H241) DENV-4 strains in mosquito cell line C6/36 (Ae. albopictus) and vertebrate cell lines Vero (African green monkey kidney) and Huh-7 (human hepatoma) (a–c, respectively). d–f: Mean virus output of human (squares) and sylvatic (diamonds) DENV-4 strains in C6/36, Vero, and Huh-7 cells (d–f, respectively); means derived from 3 strains of sylvatic and four human DENV-4 shown in panels a–c. The limit of detection of the assay is 0.9 log10 ffu/mL.
Figure 2
Figure 2. Comparative replication curves of DENV-4 strains
a–c: Daily virus output from days 0–6 following infection at MOI 0.01 by sylvatic (P73-1120, P75-215 and P75-514) and human (Haiti73, IndiaG11337, INH6412 and H241) DENV-4 strains in mosquito cell line C6/36 (Ae. albopictus) and vertebrate cell lines Vero (African green monkey kidney) and Huh-7 (human hepatoma) (a–c, respectively). d–f: Mean virus output of human (squares) and sylvatic (diamonds) DENV-4 strains in C6/36, Vero, and Huh-7 cells (d–f, respectively); means derived from 3 strains of sylvatic and four human DENV-4 shown in panels a–c. The limit of detection of the assay is 0.9 log10 ffu/mL.
Figure 2
Figure 2. Comparative replication curves of DENV-4 strains
a–c: Daily virus output from days 0–6 following infection at MOI 0.01 by sylvatic (P73-1120, P75-215 and P75-514) and human (Haiti73, IndiaG11337, INH6412 and H241) DENV-4 strains in mosquito cell line C6/36 (Ae. albopictus) and vertebrate cell lines Vero (African green monkey kidney) and Huh-7 (human hepatoma) (a–c, respectively). d–f: Mean virus output of human (squares) and sylvatic (diamonds) DENV-4 strains in C6/36, Vero, and Huh-7 cells (d–f, respectively); means derived from 3 strains of sylvatic and four human DENV-4 shown in panels a–c. The limit of detection of the assay is 0.9 log10 ffu/mL.
Figure 2
Figure 2. Comparative replication curves of DENV-4 strains
a–c: Daily virus output from days 0–6 following infection at MOI 0.01 by sylvatic (P73-1120, P75-215 and P75-514) and human (Haiti73, IndiaG11337, INH6412 and H241) DENV-4 strains in mosquito cell line C6/36 (Ae. albopictus) and vertebrate cell lines Vero (African green monkey kidney) and Huh-7 (human hepatoma) (a–c, respectively). d–f: Mean virus output of human (squares) and sylvatic (diamonds) DENV-4 strains in C6/36, Vero, and Huh-7 cells (d–f, respectively); means derived from 3 strains of sylvatic and four human DENV-4 shown in panels a–c. The limit of detection of the assay is 0.9 log10 ffu/mL.
Figure 2
Figure 2. Comparative replication curves of DENV-4 strains
a–c: Daily virus output from days 0–6 following infection at MOI 0.01 by sylvatic (P73-1120, P75-215 and P75-514) and human (Haiti73, IndiaG11337, INH6412 and H241) DENV-4 strains in mosquito cell line C6/36 (Ae. albopictus) and vertebrate cell lines Vero (African green monkey kidney) and Huh-7 (human hepatoma) (a–c, respectively). d–f: Mean virus output of human (squares) and sylvatic (diamonds) DENV-4 strains in C6/36, Vero, and Huh-7 cells (d–f, respectively); means derived from 3 strains of sylvatic and four human DENV-4 shown in panels a–c. The limit of detection of the assay is 0.9 log10 ffu/mL.
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