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Dynamic effects of antibody-dependent enhancement on the fitness of viruses

Cummings, DAT and Schwartz, IB and Billings, L and Shaw, LB and Burke, DS (2005) Dynamic effects of antibody-dependent enhancement on the fitness of viruses. Proceedings of the National Academy of Sciences of the United States of America, 102 (42). 15259 - 15264. ISSN 0027-8424

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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 non enhanced 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. © 2005 by The National Academy of Sciences of the USA.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Cummings, DAT
Schwartz, IB
Billings, L
Shaw, LB
Burke, DSdonburke@pitt.eduDONBURKE
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 18 October 2005
Date Type: Publication
Journal or Publication Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 102
Number: 42
Page Range: 15259 - 15264
DOI or Unique Handle: 10.1073/pnas.0507320102
Schools and Programs: School of Public Health > Epidemiology
Refereed: Yes
ISSN: 0027-8424
Date Deposited: 08 May 2015 15:14
Last Modified: 02 Feb 2019 16:57


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