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Advances in VIRUS RESEARCH
Advances in VIRUS RESEARCH
Date: 30 April 2011, 08:24

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CHAPTER
1
The History and Evolution of Human Dengue Emergence
Nikos Vasilakis and Scott C. Weaver
Con tents I. Introduction to Flaviviruses 2 II. Dengue Viruses 5
A. Classification of dengue viruses 5 III. Dengue Epidemiology 8
A. History of dengue virus as a human pathogen 8 B. DENV transmission cycles 21
IV. Evolution 29 A. DENV evolutionary relationships—origins and
emergence 29 B. Rates of DENV evolution 35 C. Evolution of virulence 37
V. Potential for Sylvatic Denv Reemergence 42 A. Epidemics and human contact 42 B. The influence of natural immunity or vaccination
on potential sylvatic DENV emergence 44 C. Selection pressures 47 D. Adaptation for urban transmission 49 E. Conclusions and future work 54
Acknowledgments 55
Abstra ct Dengue viruses (DENV) are the most important human arboviral pathogens. Transmission in tropical and subtropical regions of the world includes a sylvatic, enzootic cycle between nonhuman primates and arboreal mosquitoes of the genus Aedes , and an urban,
Center for Tropical Diseases and Departmen t of Pathology, Univer sity of Texas Medical Bra nch, Galveston, Texas 77555-0609
Advanc es in Viru s Research, Volume 72
2008 Elsevier Inc. ISSN 0065-3527, DOI : 10.1016/S006 5-3527(08)00401-6 All rights reser ved.
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1Nikos Vasilakis and Scott C. Weaver
endemic/epidemic cycle principally between Aedes aegypti,a mosquito that exploits peridomestic water containers as its larval habitats, and human reservoir hosts that are preferred for blood feeding. Genetic studies suggest that all four serotypes of endemic/epidemic DENV evolved independently from ancestral, sylvatic viruses and subsequently became both ecologically and evolutionarily distinct. The independent evolution of these four serotypes was accompanied by the expansion of the sylvatic progenitors’ host range in Asia to new vectors and hosts, which probably occurred gradually over a period of several hundred years. Although many emerging viral pathogens adapt to human replication and transmission, the available evidence indicates that adaptation to humans is probably not a necessary component of sylvatic DENV emergence. These findings imply that the sylvatic DENV cycles in Asia and West Africa will remain a potential source of re-emergence. Sustained urban vector control programs and/or human vaccination will be required to control DEN because the enzootic vectors and primate reservoir hosts are not amenable to interventions.
INTROD UCTION TO FLAVIVIRUSES

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