American and American/Asian genotypes of dengue virus differ in mosquito infection efficiency: candidate molecular determinants of productive vector infection

Abstract

Introduction. Genotype replacement has been associated with dramatic increases in epidemic dengue and severe dengue cases in Latin America, but little is known concerning the determinants of these genotypic sweeps. More efficient productive infection of Aedes aegypti mosquitoes could condition such sweeps. Viruses that more efficiently infect and are transmitted by mosquitoes will have a better chance of being transmitted to the next susceptible host and would thus have greater epidemic potential. Objectives. The objectives were to: determine differences in vector infection potential for DENV-2 isolates representing two DENV-2 genotypes from the Yucatan Peninsula of Mexico and to identify candidate viral molecular determinants of phenotypic differences. Materials and Methods. DENV-2 American and American/Asian isolates from the Yucatan Peninsula were characterized in vivo in mosquitoes. Midgut infection and virus dissemination to infect salivary glands for productive mosquito infection was determined by indirect inmunofluorescence assay and mosquitoes were titrated to determine viral load. The E gene and 3´ UTR were sequenced to investigate potential molecular correlates of efficient vector infection. Results. All viruses from both genotypes were equivalent in their ability to infect mosquito midguts. However, the viruses from the America/ Asian genotype efficiently disseminated to infect the salivary glands in Aedes aegypti mosquitoes but the American genotypes did not. Sequence analysis of the E protein gene and the 3’ UTR of the viruses suggested candidate molecular determinants of the vector infection phenotypes. Conclusions. DENV-2 virus genotypes differ in vector competence; American/Asian genotypes efficiently disseminate from the midgut to infect salivary glands to be transmitted. Some of the amino acid changes in E protein and nucleotides in the 3´UTR may be related to this phenotype.