%0 Journal Article
%T Phenotypic characterization of patient dengue virus isolates in BALB/c mice differentiates dengue fever and dengue hemorrhagic fever from dengue shock syndrome
%A Anne Tuiskunen
%A Maria Wahlstr£¿m
%A Jakob Bergstr£¿m
%A Philippe Buchy
%A Isabelle Leparc-Goffart
%A £¿ke Lundkvist
%J Virology Journal
%D 2011
%I BioMed Central
%R 10.1186/1743-422x-8-398
%X Three clinical DENV-1 isolates from Cambodian patients experiencing the various forms of dengue disease (DF, DHF, and DSS) were inoculated in BALB/c mice at three different concentrations. The DENV-1 isolates had different organ and cell tropism and replication kinetics. The DENV-1 isolate from a DSS patient infected the largest number of mice and was primarily neurotropic. In contrast, the DENV-1 isolates from milder clinical dengue cases infected predominantly lungs and liver, and to a lesser extent brain. In addition, infection with the DENV isolate derived from a DSS patient persisted for more than two weeks in a majority of mice compared to the other DENV-1 isolates that peaked during the first week.These results confirm the in vitro findings of the same DENV-1 isolates, that showed that the isolate derived from a DSS patient can be distinguished based on phenotypic characteristics that differ from the isolates derived from a DF and DHF case [1]. We observed in this study that the DSS virus isolate persist longer in vivo with extensive neuroinvasion in contrast to the other DENV-1 isolates originating in milder human cases. Genomic characterization of the three clinical isolates identified six amino acid substitutions unique for the DSS isolates that were located both in structural genes (M and E) and in non-structural genes (NS1, NS3, and NS5). The characterization of these clinically distinct DENV-1 isolates highlight that DENVs within the same genotype may have different in vivo phenotypes.£¿ Clinical DENV-1 isolates have different organ tropism in BALB/c mice.£¿ The isolate from a DSS patient is primarily neurotropic compared to the other isolates.£¿ The DENV-1 isolates have different in vivo replication kinetics.£¿ The isolate from a DSS patient persists longer compared to the other isolates.£¿ These phenotypic differences confirm our earlier in vitro findings with the same DENV-1 isolates. Thus, DENVs within the same serotype and genotype may differ enough to
%K dengue virus
%K mouse model
%K tropism
%K clinical isolate
%K cytokines
%K dengue hemorrhagic fever
%K flavivirus
%U http://www.virologyj.com/content/8/1/398