Dengue emergence and adaptation to peridomestic mosquitoes

Emerging Infectious Diseases,  Oct, 2004  by Abelardo C. Moncayo,  Zoraida Fernandez,  Diana Ortiz,  Mawlouth Diallo,  Amadou Sall,  Sammie Hartman,  C. Todd Davis,  Lark Coffey,  Christian C. Mathiot,  Robert B. Tesh,  Scott C. Weaver

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Current methods of dengue control rely primarily on mosquito control and are aimed at reducing the populations of urban vectors, especially Ae. aegypti. This mosquito was eradicated from much of the New World during the middle of the 20th century. After the termination of the Ae. aegypti eradication program, Ae. aegypti populations reinfested many of the New World countries from which they had been eliminated, probably from those that did not achieve eradication. Being well adapted to urban environments and competent for transmission, DENV has become the most important mosquitoborne virus in the neotropics. Air travel and migration have increased the movement of virus strains around the world. Dengue virus has frequently been imported into the United States, where local transmission has been reported (28). Much of the southern United States is at risk for dengue transmission because of the presence of endemic Ae. aegypti and Ae. albopictus. Our study suggests that local populations of both species from Galveston are highly susceptible and potentially able to transmit DENV-2 from Africa, Asia, and Oceania.

Implications for Dengue Control

Promising candidate dengue vaccines are raising hopes of effectively preventing human disease (29). Because humans are the only reservoir host for the endemic cycle, an effective vaccine could ultimately eradicate endemic strains. This scenario underscores the need for greater understanding of the historical emergence of human dengue from sylvatic origins to predict the facility with which the sylvatic strains could reemerge to initiate urban transmission. The four independent emergence events (DENV-1-4) suggest that the host-range changes that accompanied emergence can be readily accomplished by DENV; however, this hypothesis needs to be tested experimentally. One question to be answered is how many mutations are responsible for the efficient infection phenotype for Ae. aegypti and Ae. albopictus exhibited by the endemic DENV-2 strains. Identifying genetic determinants of DENV adaptation to these peridomestic vectors will ultimately provide an indication of the ability of these arboviruses to reemerge.

The viral molecular determinants that confer DENV with the ability to infect and be transmitted by their mosquito vectors are not known. Phylogenetic studies suggest that the DENV E protein may be important in the adaptation to urban vectors (11). In particular, domain III of the E protein contains several hypothetical amino acid replacements associated with emergence of urban strains. This clustering of changes in domain III is observed repeatedly during the emergence of DENV-1, DENV-2, and DENV-4, when phylogenetic methods are used. The envelope glycoproteins of other mosquitoborne viruses, including Sindbis (30), Venezuelan equine encephalitis (31-33), and La Crosse viruses (34), have been shown to mediate vector infection. Another genomic region potentially important in mediating vector transmission may be the 5' noncoding region. Deletions in this region of DENV4 constrain its ability to infect Ae. aegypti and Ae. albopictus mosquitoes (35).