title: Potential of ancestral sylvatic dengue-2 viruses to re-emerge.
abstract: Dengue viruses (DENV) are the most important arboviral pathogens in tropical and subtropical regions throughout the world. DENV transmission includes both a sylvatic, enzootic cycle between nonhuman primates and arboreal mosquitoes of the genus Aedes, and an urban, endemic/epidemic cycle between Aedes aegypti, a mosquito with larval development in peridomestic water containers, and human reservoir hosts. All 4 serotypes of endemic DENV evolved independently from ancestral sylvatic viruses and have become both ecologically and evolutionarily distinct; this process may have involved adaptation to (i) peridomestic mosquito vectors and/or (ii) human reservoir hosts. To test the latter hypothesis, we assessed the ability of sylvatic and endemic DENV-2 strains, representing major genotypes from Southeast Asia, West Africa and the Americas, to replicate in two surrogate human model hosts: monocyte-derived, human dendritic cells (moDCs), and mice engrafted with human hepatoma cells. Although the various DENV-2 strains showed significant inter-strain variation in mean replication titers in both models, no overall difference between sylvatic and endemic strains was detected in either model. Our findings suggest that emergence of endemic DENV strains from ancestral sylvatic strains may not have required adaptation to replicate more efficiently in human reservoir hosts, implying that the potential for re-emergence of sylvatic dengue strains into the endemic cycle is high. The shared replication profiles of the American endemic and sylvatic strains suggest that American strains have maintained or regained the ancestral phenotype.
authors.affiliation: Center for Biodefense and Emerging Infectious Diseases and Department of Pathology, University of Texas Medical Branch, Keiller Bldg, Rm 3.135, 301 University Boulevard, Galveston, TX 77555-0609, USA.
authors.forename: Nikos
authors.initials: N
authors.lastname: Vasilakis
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Shell
authors.forename: Eric B
authors.initials: EB
authors.lastname: Fokam
authors.forename: Peter W
authors.initials: PW
authors.lastname: Mason
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Hanley
authors.forename: D Mark
authors.initials: DM
authors.lastname: Estes
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells; D003715:Dengue / Q000821:virology*; D003716:Dengue Virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D010802:Phylogeny; D014183:Transplantation, Heterologous; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: D014759:Viral Envelope Proteins