Dynamic Effects of Antibody-Dependent Enhancement on the Fitness of Viruses

Antibody-dependent enhancement (ADE), a phenomenon in which viral replication is increased rather than decreased by immune sera, has been observed in vitro for a large number of viruses of public health importance, including flaviviruses, coronaviruses, and retroviruses. The most striking in vivo ex...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-10, Vol.102 (42), p.15259-15264
Main Authors: Derek A. T. Cummings, Schwartz, Ira B., Lora Billings, Leah B. Shaw, Burke, Donald S.
Format: Article
Language:English
Subjects:
Animals
Antibody-Dependent Enhancement
Biological Sciences
Coinfection
Dengue
Dengue virus
Dengue Virus - immunology
Disease models
Disease transmission
Epidemiology
Humans
Immune Sera
Immunity
Infections
Models, Theoretical
Mortality
Public health
Serotyping
Severe Dengue - blood
Severe Dengue - epidemiology
Viral diseases
Virus Replication
Viruses
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Summary:Antibody-dependent enhancement (ADE), a phenomenon in which viral replication is increased rather than decreased by immune sera, has been observed in vitro for a large number of viruses of public health importance, including flaviviruses, coronaviruses, and retroviruses. The most striking in vivo example of ADE in humans is dengue hemorrhagic fever, a disease in which ADE is thought to increase the severity of clinical manifestations of dengue virus infection by increasing virus replication. We examine the epidemiological impact of ADE on the prevalence and persistence of viral serotypes. Using a dynamical system model of n cocirculating dengue serotypes, we find that ADE may provide a competitive advantage to those serotypes that undergo enhancement compared with those that do not, and that this advantage increases with increasing numbers of cocirculating serotypes. Paradoxically, there are limits to the selective advantage provided by increasing levels of ADE, because greater levels of enhancement induce large amplitude oscillations in incidence of all dengue virus infections, threatening the persistence of both the enhanced and nonenhanced serotypes. Although the models presented here are specifically designed for dengue, our results are applicable to any epidemiological system in which partial immunity increases pathogen replication rates. Our results suggest that enhancement is most advantageous in settings where multiple serotypes circulate and where a large host population is available to support pathogen persistence during the deep troughs of ADE-induced large amplitude oscillations of virus replication.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0507320102