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Dengue Virus Type 3 Isolated from a Fatal Case with Visceral Complications Induces Enhanced Proinflammatory Responses and Apoptosis of Human Dendritic Cells▿†
- Publication Year :
- 2011
- Publisher :
- American Society for Microbiology, 2011.
-
Abstract
- A recent (2007 to 2009) dengue outbreak caused by dengue virus (DENV) in Paraguay presented unusual severe clinical outcomes associated with 50% mortality rates. Although it has been reported that inflammatory responses influence the severity of dengue virus infection (T. Pang, M. J. Cardosa, and M. G. Guzman, Immunol. Cell Biol. 85:43–45, 2007), there remains a paucity of information on virus-innate immunity interactions influencing clinical outcome. Using human dendritic cells from a major innate immune cell population as an in vitro model, we have investigated signature cytokine responses as well as infectivity-replicative profiles of DENV clinical isolates from either a nonfatal case of classical dengue fever (strain DENV3/290; isolated in Brazil in 2002) or a fatal case of dengue fever with visceral complications isolated in Paraguay in 2007 (strain DENV3/5532). Strain DENV3/5532 was found to display significantly higher replicative ability than DENV3/290 in monocyte-derived dendritic cells (mdDCs). In addition, compared to DENV3/290 results, mdDCs exposed to DENV3/5532 showed increased production of proinflammatory cytokines associated with higher rates of programmed cell death, as shown by annexin V staining. The observed phenotype was due to viral replication, and tumor necrosis factor alpha (TNF-α) appears to exert a protective effect on virus-induced mdDC apoptosis. These results suggest that the DENV3/5532 strain isolated from the fatal case replicates within human dendritic cells, modulating cell survival and synthesis of inflammatory mediators.
- Subjects :
- Immunology
Molecular Sequence Data
Cellular Response to Infection
Apoptosis
Dengue virus
medicine.disease_cause
Virus Replication
Microbiology
Virus
Proinflammatory cytokine
Dengue fever
Dengue
Virology
medicine
Humans
Antibody-dependent enhancement
Innate immune system
biology
Dendritic cell
Dendritic Cells
Sequence Analysis, DNA
Dengue Virus
biology.organism_classification
medicine.disease
Flavivirus
Paraguay
Insect Science
Cytokines
RNA, Viral
Brazil
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....13c950c6aa9239c7084bdc8f3dc6ce03