Genetic variation among Aedes aegypti populations can greatly influence their vector competence for human pathogens such as the dengue virus (DENV). While intra-species transcriptome differences remain relatively unstudied when compared to coding sequence polymorphisms, they also affect numerous aspects of mosquito biology. Comparative molecular profiling of mosquito strain transcriptomes can therefore provide valuable insight into the regulation of vector competence. We established a panel of A. aegypti strains with varying levels of susceptibility to DENV, comprising both laboratory-maintained strains and field-derived colonies collected from geographically distinct dengue-endemic regions spanning South America, the Caribbean, and Southeast Asia. A comparative genome-wide gene expression microarray-based analysis revealed higher basal levels of numerous immunity-related gene transcripts in DENV-refractory mosquito strains than in susceptible strains, and RNA interference assays further showed different degrees of immune pathway contribution to refractoriness in different strains. By correlating transcript abundance patterns with DENV susceptibility across our panel, we also identified new candidate modulators of DENV infection in the mosquito, and we provide functional evidence for two potential DENV host factors and one potential restriction factor. Our comparative transcriptome dataset thus not only provides valuable information about immune gene regulation and usage in natural refractoriness of mosquito populations to dengue virus but also allows us to identify new molecular interactions between the virus and its mosquito vector.

This is among the first estimates of R0 for a ZIKV outbreak in the Americas, and also among the first quantifications of the relative impact of sexual transmission.

The global emergence of Zika virus (ZIKV) revealed the unprecedented ability for a mosquito-borne virus to cause congenital birth defects. A puzzling aspect of ZIKV emergence is that all human outbreaks and birth defects to date have been exclusively associated with the Asian ZIKV lineage, despite a growing body of laboratory evidence pointing towards higher transmissibility and pathogenicity of the African ZIKV lineage. Whether this apparent paradox reflects the use of relatively old African ZIKV strains in most laboratory studies is unclear. Here, we experimentally compare seven low-passage ZIKV strains representing the recently circulating viral genetic diversity. We find that recent African ZIKV strains display higher transmissibility in mosquitoes and higher lethality in both adult and fetal mice than their Asian counterparts. We emphasize the high epidemic potential of African ZIKV strains and suggest that they could more easily go unnoticed by public health surveillance systems than Asian strains due to their propensity to cause fetal loss rather than birth defects.

The drivers and patterns of zoonotic virus emergence in the human population are poorly understood. The mosquito Aedes aegypti is a major arbovirus vector native to Africa that invaded most of the world’s tropical belt over the past four centuries, after the evolution of a “domestic” form that specialized in biting humans and breeding in water storage containers. Here, we show that human specialization and subsequent spread of A. aegypti out of Africa were accompanied by an increase in its intrinsic ability to acquire and transmit the emerging human pathogen Zika virus. Thus, the recent evolution and global expansion of A. aegypti promoted arbovirus emergence not solely through increased vector–host contact but also as a result of enhanced vector susceptibility.

We compared dengue virus (DV) isolation rates and tested whether acute primary (P) and acute/probable acute secondary (S/PS) DV infections could be correctly classified serologically when the patients' first serum (S1) samples were obtained 1 to 3 days after the onset of symptoms (AOS). DV envelope/membrane proteinspecific immunoglobulin M (IgM) capture and IgG capture enzyme-linked immunosorbent assay (ELISA) titrations (1/log 10 1.7 to 1 log 10 6.6 dilutions) were performed on 100 paired S1 and S2 samples from suspected DV infections. The serologically confirmed S/PS infections were divided into six subgroups based on their different IgM and IgG responses. Because of their much greater dynamic ranges, IgG/IgM ELISA titer ratios were more accurate and reliable than IgM/IgG optical density (OD) ratios recorded at a single cutoff dilution for discriminating between P and S/PS infections. However, 62% of these patients' S1 samples were DV IgM and IgG titer negative (2.60 and <2.60) discriminatory IgM/IgG OD (DOD) ratios on these S1 samples than those published previously to correctly classify the highest percentage of these P and S/PS infections. The DV isolation rate was highest (12/12; 100%) using IgG and IgM titer-negative S1 samples collected 1 day AOS, when 100% of them were correctly classified as P or S/PS infections using these higher DOD ratios.The dengue viruses (DVs) are flaviviruses contained within their own antigenic complex of four serotypes defined by neutralization assays, and therefore, patients can encounter sequential (secondary) infections with different DV serotypes. The diagnosis of these viruses generally relies on virus isolation (cell culture) or the detection of viral RNA using reverse transcription-PCR and serological assays (20,23,24). DV surveillance programs also require virus isolates for subsequent comparisons with other DV strains (e.g., cDNA sequence determination and phylogenetic analyses). For this purpose, patients' sera must be obtained early in the acute phase of disease before the virus is neutralized by their rising titers of antibody. DV isolation is therefore usually unsuccessful using patients' sera obtained 6 or more days after the onset of symptoms (23). Thus, while DVs can be efficiently isolated from patients' sera collected early after the onset of symptoms, these sera are often DV-specific immunoglobulin M (IgM) and IgG titer negative in serological assays (10,11,14,20,21,23). In addition to this first serum (S1) sample, a second serum (S2) sample, obtained 2 to 14 days afterwards, is therefore usually required to confirm a Ն4-fold increase in DV envelope/membrane (E/M) protein-specific titers of IgG or IgM and to classify infections as either acute primary (P) or secondary (S) flaviv...