Under-the-radar dengue virus infections in natural populations of Aedes aegypti mosquitoes

Abstract

<jats:title>Abstract</jats:title><jats:p>The incidence of locally acquired dengue infections increased during the last decade in the United States, compelling a sustained research effort on the dengue mosquito vector, <jats:italic>Aedes aegypti,</jats:italic> and its microbiome, which has been shown to influence virus transmission success. We examined the ‘metavirome’ of four populations of <jats:italic>Ae. aegypti</jats:italic> mosquitoes collected in 2016-2017 from Manatee County, Florida. Unexpectedly, we discovered that dengue virus serotype 4 (DENV4) was circulating in these mosquito populations, representing the first documented case of such a phenomenon in the absence of a local DENV4 human case in this county over a two-year period. We confirmed that all of the mosquito populations carried the same DENV4 strain, assembled its full genome, validated infection orthogonally by reverse transcriptase PCR, traced the virus origin, estimated the time period of its introduction to the Caribbean region, as well as explored the viral genetic signatures and mosquito-specific virome associations that potentially mediated DENV4 persistence in mosquitoes. We discuss the significance of prolonged maintenance of these DENV4 infections in <jats:italic>Ae. aegypti</jats:italic> that occurred in the absence of a DENV4 human index case in Manatee County with respect to the inability of current surveillance paradigms to detect mosquito vector infections prior to a potential local outbreak.</jats:p><jats:sec><jats:title>Importance</jats:title><jats:p>Since 1999, dengue outbreaks in the continental United States (U.S.) involving local transmission have occurred episodically and only in Florida and Texas. In Florida, these episodes appear to be coincident with increased introductions of dengue virus into the region through human travel and migration from endemic countries. To date, the U.S. public health response to dengue outbreaks is largely reactive, and implementation of comprehensive arbovirus surveillance in advance of predictable transmission seasons, which would enable proactive preventative efforts, remains unsupported. The significance of our finding is that it is the first documented report of non-outbreak DENV4 transmission and maintenance within a local mosquito vector population in the continental U.S.in the absence of a human case during a two-year time period. Our data suggest that molecular surveillance of mosquito populations in high-risk, high tourism areas of the U.S., may allow for proactive, targeted vector control before potential arbovirus outbreaks.</jats:p></jats:sec>

Metagenomic analysis of Aedes aegypti and Culex quinquefasciatus mosquitoes from Grenada, West Indies

“…No major human pathogens transmitted by C. quinquefasciatus have been reported in Grenada, but the mosquito is capable of transmitting several arboviruses that occur in other Caribbean islands (e.g., WNV, St. Louis Encephalitis virus) or in neighboring mainland South American countries (e.g., Wuchereria bancrofti) [17]. The microbial composition of A. aegypti and C. quinquefasciatus mosquitoes has been previously studied [18,19,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. However, several arthropod-borne diseases that are endemic to the mainland Americas are not believed to be established in Caribbean islands (e.g.…”

Geographic partitioning of dengue virus transmission risk in Florida

“…At the nucleotide and amino acid level, DENV-2 and DENV-4 are the most divergent among the four serotypes, with DENV-1 and DENV-3 being most similar [51][52][53]. In particular, DENV-4 WT and DENV-4 L share 93% nucleotide identity and 98% amino acid identity but the DENV-4 L sequence has an additional 15 nucleotides in its 3' UTR not seen in contemporary strains within genotype IIb [40]. We suspect that certain genetic changes arising from continuous cell culture of the DENV laboratory stocks could be responsible for their lower fitness in Ae.…”

“…We previously identified and fully sequenced a DENV-4 strain with high identity to our DENV-4 WT from Haiti in Ae. aegypti from Manatee Co. in 2016 and 2017, in the absence of a human case across both years [40]. It is possible that there were unreported asymptomatic dengue cases [57], but this cannot be known with certainty unless paired with serology studies.…”

“…Manatee Co. in southwest FL was classified as "medium risk" because there was a report of dengue-positive Ae. aegypti (DENV-4) in 2016 and 2017, but no previous local dengue transmission was detected since 2009 [40]. Miami-Dade Co. in south FL was classified as "high risk" because there have been reports of both dengue-positive mosquito pools (unpublished) and human dengue cases in multiple years since 2009 [30,33].…”

Landscape and Anthropogenic Factors Associated with Adult Aedes aegypti and Aedes albopictus in Small Cities in the Southern Great Plains

“…The emergence and repeated expansion of vector-borne human and animal diseases worldwide, and the increasing pace at which epidemics seem to occur, emphasize the continued need to surveille important disease vectors to prevent or respond to outbreaks. The recent rapid expansion of Chikungunya, Dengue, and Zika viruses through Aedes mosquitoes in Central and South America and the Caribbean region has focused attention on potential regions in the United States where epidemics could occur [ 2 , 3 , 4 , 5 ]. To mitigate potential outbreaks, studies have broadly mapped potential regions where two important vectors, Aedes albopictus (Skuse) and Ae.…”