Evolutionary Relationships of Endemic/Epidemic and Sylvatic Dengue Viruses

Abstract

Endemic/epidemic dengue viruses (DEN) that are transmitted among humans by the mosquito vectors Aedes aegypti and Aedes albopictus are hypothesized to have evolved from sylvatic DEN strains that are transmitted among nonhuman primates in West Africa and Malaysia by other Aedes mosquitoes. We tested this hypothesis with phylogenetic studies using envelope protein gene sequences of both endemic/epidemic and sylvatic strains. The basal position of sylvatic lineages of DEN-1, -2, and -4 suggested that the endemic/epidemic lineages of these three DEN serotypes evolved independently from sylvatic progenitors. Time estimates for evolution of the endemic/epidemic forms ranged from 100 to 1,500 years ago, and the evolution of endemic/epidemic forms represents relatively recent events in the history of DEN evolution. Analysis of envelope protein amino acid changes predicted to have accompanied endemic/epidemic emergence suggested a role for domain III in adaptation to new mosquito and/or human hosts.Dengue viruses (DEN) (Flaviviridae: Flavivirus) are serious human pathogens that occur nearly throughout the tropics, with ca. 100 million cases annually (16). DEN comprise four serotypes (DEN-1 to DEN-4); although epidemiologically similar, they are genetically and antigenically distinct. Infection with one serotype leads to lifelong protection against homologous reinfection but only brief protection against heterologous challenge (21, 38).DEN cause dengue fever, a self-limited febrile illness lasting 2 to 10 days that has been known in the medical literature for over 200 years. Infrequent epidemics of dengue fever occurred in tropical areas until the 1950s. After War World II, this pattern of disease was disrupted by the emergence of dengue hemorrhagic fever and dengue shock syndrome, more severe diseases characterized by thrombocytopenia, hemorrhage, and excessive plasma leakage (16,28). Two principal hypotheses have been proposed to explain the hemorrhagic form of disease: (i) the immune enhancement theory maintains that hemorrhage occurs in secondary infections when DEN-specific antibodies and memory T cells resulting from primary infection with another serotype enhance the binding of virus-immunoglobulin G complexes to FcY receptors on monocytic cells, and (ii) certain phenotypes of DEN are more virulent than others. Recent phylogenetic studies suggest that an Asian genotype of DEN-2 recently introduced into the New World may be associated with increased risk for hemorrhagic fever and shock in the presence of heterologous antibody (32). DEN strains of reduced virulence have also been described; endemic transmission on the South Pacific islands of Tonga, involving vectors other than Aedes aegypti, may result in less severe disease because of the lesser selection for high viremia imposed by more susceptible vectors, like Aedes polynesiensis (13). Two distinct DEN transmission cycles occur: (i) endemic and epidemic DEN involving human hosts and transmission byA. aegypti, with Aedes albopictus and other Aedes mosquitoes serv...

Dengue: a continuing global threat

“…DENV-1-4 evolved in non-human primates from a common ancestor and each entered the urban cycle independently an estimated 500-1,000 years ago 12 . The virion comprises a spherical particle, 40-50 nm in diameter, with a lipopolysaccharide envelope.…”

Models of dengue virus infection

“…These models have shown that specific dengue virus genetic variants or genotypes have established transmission cycles on other continents, are responsible for outbreaks of more severe disease (DHF/DSS) and have helped track the displacement of one genotype by another, more virulent genotype. However, some of these algorithms have also been used to extrapolate on the occurrence of intramolecular recombination in dengue RNA genomes [44], the ancient origin of epidemic strains [45] and the movement of genotypes within a country or from one country to another [46], without the support of molecular studies of viruses or sufficient field sampling and epidemiologic studies of the transmission cycles. Therefore, it is unclear whether these phenomena actually occur in nature.…”

RNAi: antiviral therapy against dengue virus

“…DENV is a member of Flaviviridae family and is transmitted to humans by infected female Aedes genus, especially Aedes aegypti or Aedes albopictus [3,4] . There are four serotypes of dengue virus (DENV [1][2][3][4] that manifest with similar symptoms [5,6] . Two types of infections are caused by DENV, namely, primary infection and secondary infection.…”