Abstract
BackgroundSeveral studies have shown that American genotype dengue 2 viruses (DENV2) have reduced viral fitness in the mosquito vector, Aedes aegypti, compared to other DENV2 genotypes. Diminished replication efficiency or inability to efficiently traverse membrane barriers encompassing organs such as the midgut or salivary glands are considered major factors negatively impacting viral fitness in the mosquito.ResultsWe analyzed the vector competence of Ae. aegypti for two American DENV2 strains, QR94 and PR159 originating from Mexico and Puerto-Rico, respectively. Both strains infected mosquito midguts following acquisition of infectious bloodmeals. However, DENV2-QR94 and DENV2-PR159 poorly disseminated from the midgut at 7 or 14 days post-bloodmeal (pbm). We detected one virus isolate, EM33, among 31 DENV2-QR94 infected mosquitoes, and one isolate, EM41, among 121 DENV2-PR159 infected mosquitoes, generating high virus titers in mosquito carcasses at 7 days pbm. In oral challenge experiments, EM33 and EM41 showed midgut dissemination rates of 40-50%. Replication efficiency of EM41 in secondary mosquito tissue was similar to that of a dissemination-competent control strain, whereas the replication efficiency of EM33 was significantly lower than that of the control virus. The genome sequence of DENV2-QR94 encoded seven unique amino acids (aa), which were not found in 100 of the most closely related DENV2 strains. EM33 had one additional aa change, E202K, in the E protein. DENV2-PR159 encoded four unique aa residues, one of them E202K, whereas EM41 had two additional aa substitutions, Q77E in the E protein and E93D in NS3.ConclusionsOur results indicate that the midgut of Ae. aegypti acts as a selective sieve for DENV2 in which genetically distinct, dissemination-competent virus variants are rapidly selected from the viral quasispecies to be transmitted to vertebrates.
Highlights
Several studies have shown that American genotype dengue 2 viruses (DENV2) have reduced viral fitness in the mosquito vector, Aedes aegypti, compared to other DENV2 genotypes
We show that DENV2-QR94 and PR159 dissemination from the mosquito midgut is inhibited in the laboratory–adapted Higgs White Eye (HWE) strain of Ae. aegypti
Phylogenetic characterization of DENV2-QR94 and DENV2-PR159 The PR159 and QR94 strains have been assigned to the American genotype of DENV2 based on 240 bp nucleotide sequences from their E/NS1 gene region [26,27]
Summary
Several studies have shown that American genotype dengue 2 viruses (DENV2) have reduced viral fitness in the mosquito vector, Aedes aegypti, compared to other DENV2 genotypes. The virus can encounter a midgut infection barrier (MIB), which restricts its ability to invade the epithelial cells for replication [9]. Another major barrier that has been investigated is the midgut escape barrier (MEB) [10,11]. In this case the virus is unable to efficiently disseminate from the midgut following efficient replication in the epithelial cells. Less efficient vector transmission of American genotype DENV2 strains has been associated with less efficient dissemination from the mosquito midgut to secondary tissues [19,21].
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