Apoptotic cell death in response to dengue virus infection: the pathogenesis of dengue haemorrhagic fever revisited.
BACKGROUND
Dengue virus infection may be asymptomatic or lead to undifferentiated febrile illness or dengue haemorrhagic fever and dengue shock syndrome (DHF/DSS). The major clinical manifestations of DHF/DSS are high fever, haemorrhage, hepatomegaly and circulatory failure.


OBJECTIVE
The relatively high level of viraemia only a few days after infection may reflect a large number of replication sites. However, the degree of cell injury in fatal cases of DHF/DSS is not sufficient to explain death and suggests metabolic disturbance rather than tissue destruction. This theory was investigated in this study.


RESULTS
We demonstrated that replication of dengue virus in infected cells induces stress leading to apoptotic cell death in vitro and in vivo.


CONCLUSIONS
The elimination of apoptotic bodies by phagocytic cells is a previously unsuspected pathway of dengue virus clearance from infected tissues. However, the mechanisms of host defence involving apoptosis and phagocytic cell activation may cause local tissue injury or transient homeostasis imbalance and may trigger further deleterious events.
Marianneau
P
P
Unité des Arbovirus et Virus des Fièvres Hémorragiques, Institut Pasteur, Paris, France.
Flamand
M
M
Deubel
V
V
Desprès
P
P
D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000096:biosynthesis; D003716:Dengue Virus / Q000472:pathogenicity*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000821:virology; D009474:Neurons / Q000821:virology; D010587:Phagocytosis; D019595:Severe Dengue / Q000276:immunology / Q000503:physiopathology*
D016207:Cytokines