title: Dengue virus type 3 isolated from a fatal case with visceral complications induces enhanced proinflammatory responses and apoptosis of human dendritic cells.
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.
authors: Laboratório de Virologia Molecular, Instituto Carlos Chagas, FIOCRUZ, Curitiba, PR, Brazil.
authors: Guilherme F
authors: GF
authors: Silveira
authors: Florencia
authors: F
authors: Meyer
authors: Adriana
authors: A
authors: Delfraro
authors: Ana Luiza P
authors: AL
authors: Mosimann
authors: Norma
authors: N
authors: Coluchi
authors: Cyntia
authors: C
authors: Vasquez
authors: Christian M
authors: CM
authors: Probst
authors: André
authors: A
authors: Báfica
authors: Juliano
authors: J
authors: Bordignon
authors: Claudia N Duarte
authors: CN
authors: Dos Santos
mesh_terms: D017209:Apoptosis; D001938:Brazil; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D003715:Dengue / Q000821:virology*; D003716:Dengue Virus / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D010239:Paraguay; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D014779:Virus Replication
chemical_list: D016207:Cytokines; D012367:RNA, Viral