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Sci Transl Med DOI:10.1126/scitranslmed.3003084

Dynamics of dengue disease severity determined by the interplay between viral genetics and serotype-specific immunity.

Publication TypeJournal Article
Year of Publication2011
AuthorsOhAinle, M, Balmaseda, A, Macalalad, AR, Tellez, Y, Zody, MC, Saborío, S, Nuñez, A, Lennon, NJ, Birren, BW, Gordon, A, Henn, MR, Harris, E
JournalSci Transl Med
Date Published2011 Dec 21
KeywordsDengue, Dengue Virus, Humans, Molecular Sequence Data, Severity of Illness Index

The rapid spread of dengue is a worldwide public health problem. In two clinical studies of dengue in Managua, Nicaragua, we observed an abrupt increase in disease severity across several epidemic seasons of dengue virus serotype 2 (DENV-2) transmission. Waning DENV-1 immunity appeared to increase the risk of severe disease in subsequent DENV-2 infections after a period of cross-protection. The increase in severity coincided with replacement of the Asian/American DENV-2 NI-1 clade with a new virus clade, NI-2B. In vitro analyses of viral isolates from the two clades and analysis of viremia in patient blood samples support the emergence of a fitter virus in later, relative to earlier, epidemic seasons. In addition, the NI-1 clade of viruses was more virulent specifically in children who were immune to DENV-1, whereas DENV-3 immunity was associated with more severe disease among NI-2B infections. Our data demonstrate that the complex interaction between viral genetics and population dynamics of serotype-specific immunity contributes to the risk of severe dengue disease. Furthermore, this work provides insights into viral evolution and the interaction between viral and immunological determinants of viral fitness and virulence.


Alternate JournalSci Transl Med
PubMed ID22190239
PubMed Central IDPMC4517192
Grant ListR01 GM087405 / GM / NIGMS NIH HHS / United States
HHSN272200900018C / AI / NIAID NIH HHS / United States
R42 AI062100 / AI / NIAID NIH HHS / United States
R41 AI062100 / AI / NIAID NIH HHS / United States
HHSN272200900006C / AI / NIAID NIH HHS / United States
U54 AI065359 / AI / NIAID NIH HHS / United States