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

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 t...

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Published inScience translational medicine Vol. 3; no. 114; p. 114ra128
Main Authors OhAinle, Molly, Balmaseda, Angel, Macalalad, Alexander R, Tellez, Yolanda, Zody, Michael C, Saborío, Saira, Nuñez, Andrea, Lennon, Niall J, Birren, Bruce W, Gordon, Aubree, Henn, Matthew R, Harris, Eva
Format Journal Article
LanguageEnglish
Published United States 21.12.2011
Subjects
Dengue - pathology
Dengue Virus - genetics
Dengue Virus - immunology
Humans
Molecular Sequence Data
Severity of Illness Index
Online AccessGet more information

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Abstract 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.
AbstractList 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.
Author Zody, Michael C
Harris, Eva
Lennon, Niall J
Nuñez, Andrea
Birren, Bruce W
Gordon, Aubree
Tellez, Yolanda
OhAinle, Molly
Saborío, Saira
Balmaseda, Angel
Macalalad, Alexander R
Henn, Matthew R
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Snippet 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...
SourceID pubmed
SourceType Index Database
StartPage 114ra128
SubjectTerms Dengue - pathology
Dengue Virus - genetics
Dengue Virus - immunology
Humans
Molecular Sequence Data
Severity of Illness Index
Title Dynamics of dengue disease severity determined by the interplay between viral genetics and serotype-specific immunity
URI https://www.ncbi.nlm.nih.gov/pubmed/22190239
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