Bloody Virus

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Science  27 Jun 2003:
Vol. 300, Issue 5628, pp. 2005
DOI: 10.1126/science.300.5628.2005d

The mosquito-born flavivirus that causes dengue fever threatens 50 million people a year. A first infection can be shrugged off after a febrile illness, but subsequent infection with one of the other four serotypes can result in dengue hemorrhagic fever, which in 20% of cases proves fatal. This double jeopardy is a major obstacle to vaccine design. In secondary infections, preexisting antibodies, which do not neutralize the virus, bind to virus particles and promote their uptake into macrophages where they replicate and amplify viremia and hence disease severity, which correlates with viral load. Mongkolsapaya et al. have made the connection to pathophysiology in studies on hospitalized Thai children. In these patients, instead of killing virus, the cytotoxic CD8+ cells become “stunned” and cease to produce protective interferon gamma. In severely affected children with a history of serial dengue infections, the frequency of antigen-specific T cells for the current serotype was unexpectedly low, but a high frequency of apoptotic T cells was found. Somehow secondary infection sees an expansion of low-affinity, cross-reacting T cells, possibly because the high viral load drives high-affinity T cells into apoptosis, releasing large amounts of cytokines into the blood system. It is the flood of cytokines that causes the cell damage and hemorrhagic symptoms.—CA

Nature Medicine 10.1038/nm887 (2003).

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