Phenotypic and genotypic characterization of dengue virus isolates differentiates dengue fever and dengue hemorrhagic fever from dengue shock syndrome

Abstract

Dengue viruses (DENV) cause 50-100 million cases of acute febrile disease every year, including 500,000 reported cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Viral factors have been proposed to influence the severity of the disease, but markers of virulence have never been identified on DENV. Three DENV serotype-1 isolates from the 2007 epidemic in Cambodia that are derived from patients experiencing the various clinical forms of dengue were characterized both phenotypically and genetically. Phenotypic characteristics in vitro, based on replication kinetics in different cell lines and apoptosis response, grouped isolates from DF and DHF patients together, whereas the virus isolate from a DSS patient showed unique features: a lower level of replication in mammalian cells and extensive apoptosis in mosquito cells. Genomic comparison of viruses revealed six unique amino acid residues in the membrane, envelope, and in non-structural genes in the virus isolated from the DSS patient.

Phenotypic characterization of patient dengue virus isolates in BALB/c mice differentiates dengue fever and dengue hemorrhagic fever from dengue shock syndrome

“…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.…”

Circulation of Dengue Virus Serotypes in the City of Makkah, Saudi Arabia, as Determined by Reverse Transcription Polymerase Chain Reaction

“…In a previous study by Khan et al [10] higher prevalence of the DENV-2 serotype was reported in contrast to the DENV-3 in DF cases in Makkah, with no DENV-1 detection. DENV-1 appears to be the predominant dengue virus serotype in various regions, as it was the frequently detected DENV serotype in DF/DHF/DSS cases in the endemic areas of the Middle East, Asia, South America, or even in the nondengue endemic countries, such as Japan, where DENV is introduced by the travelers coming from the endemic regions [6, 16–18]. On the whole, it appears that DENV-3 has least circulation not only in the cases tested in current study, but also in the other patients belonging to the different areas in Saudi Arabia [7, 8, 10, 19] and elsewhere [20].…”

An emerging role for the anti-inflammatory cytokine interleukin-10 in dengue virus infection

“…Many reports have suggested that the viral genotypic nucleotide variation is associated with disease severity [40,41]. In addition, higher levels of plasma DENV RNA have been observed in DHF patients compared with DF patients [42,43].…”