Dengue is the most important reemerging mosquito-borne viral disease worldwide. It is caused by any of four Dengue virus types or serotypes (DENV-1 to DENV-4) and is transmitted by mosquitoes from the genus Aedes. Ecological changes have favored the geographic expansion of the vector and, since the dengue pandemic in the Asian and Pacific regions, the infection became widely distributed worldwide, reaching Brazil in 1845. The incidence of dengue in Brazil has been frequently high, and the number of cases in the country has at some point in time represented up to 60% of the dengue reported cases worldwide. This review addresses vector distribution, dengue outbreaks, circulating serotypes and genotypes, and prevention approaches being utilized in Brazil.

Dengue virus (DENV) is an arbovirus transmitted to humans byAedes mosquitoes 1 . In the insect vector, the small interfering RNA (siRNA) pathway is an important antiviral mechanism against DENV 2-5 . However, it remains unclear when and where the siRNA pathway acts during the virus cycle. Here, we show that the siRNA pathway fails to efficiently silence DENV in the midgut of Aedes aegypti although it is essential to restrict systemic replication. Accumulation of DENV-derived siRNAs in the midgut reveals that impaired silencing results from a defect downstream of small RNA biogenesis. Notably, silencing triggered by endogenous and exogenous dsRNAs remained effective in the midgut where known components of the siRNA pathway, including the dsRNA binding proteins Loquacious and r2d2, had normal expression levels. We identified an Aedes specific paralog of loquacious and r2d2, hereafter named loqs2, which is not expressed in the midgut. Loqs2 interacts with Loquacious and r2d2 and is required to control systemic replication of DENV and also Zika virus (ZIKV). Furthermore, ectopic expression of Loqs2 in the midgut of transgenic mosquitoes is sufficient to restrict DENV replication and dissemination. Together our data reveal a mechanism of tissue specific regulation of the mosquito siRNA pathway controlled by Loqs2.Previous studies observed production of DENV-derived siRNAs and piwi-interacting RNAs (piRNAs) in infected mosquitoes and suggested that different RNA interference (RNAi) mechanisms were important to control virus replication 2,3,6,7 . In order to investigate the activation of RNAi by DENV infection in mosquitoes, we first analyzed different concentrations of the virus in the blood meal (Supplementary Fig. 1a,b). Using 10 7 PFU/mL of virus, we observed that 100% of individual mosquitoes had detectable virus at 1 and 2 days post feeding (dpf) (Fig. 1a). This likely corresponds to the virus inoculum in the blood meal since the amount of viral RNA decreased until 4 dpf when mosquitoes have completed blood digestion 8 . At this point, viral RNA could not be detected in some mosquitoes, suggesting that they had cleared the virus (defined

Aedes aegypti and Aedes albopictus mosquitoes are the main vectors for dengue virus (DENV) and other arboviruses, including Zika virus (ZIKV).Understanding the factors that affect transmission of arboviruses from mosquitoes to humans is a priority, because it could inform public health and targeted interventions. Reasoning that interactions among viruses

The mosquito Stegomyia albopicta is among the most important arbovirus vectors in the world, particularly for Dengue viruses. Their natural history suggests that biologically these viruses are highly adapted to their mosquito hosts and they were most likely mosquito viruses prior to becoming adapted to lower primates and humans. As well as being maintained by transmission among susceptible humans, Dengue viruses may also be maintained by vertical transmission in mosquitoes during inter-epidemic periods. The larvae and mosquitoes of Stegomyia albopicta were used to identify the vertical transmission of the dengue virus in nature and to confirm the vectorial capacity concerning the Dengue virus type 2 infection. The minimum infection rate concerning S. albopicta infection with the Dengue virus was 1:36.45. In Brazil this was the first time that high minimum infection rates of vertical transmission of S. albopicta were detected in this species.Keywords: Dengue virus, vertical transmission, Stegomyia albopicta, vectorial capacity. Transmissão vertical natural de Stegomyia albopicta como vetor de dengue no BrasilResumo O mosquito Stegomyia albopicta está dentre os mais importantes vetores de arbovírus do mundo, particularmente para o Dengue virus. A história natural sugere que biologicamente esses vírus são altamente adaptados aos seus mosquitos vetores e foram, provavelmente, os vírus que infectavam mosquitos antes de se tornarem adaptados a primatas não humanos e humanos. Além de serem mantidos entre os homens susceptíveis, os Dengue viruses podem também ser mantidos pela transmissão vertical em mosquitos durante os períodos interepidêmicos. As larvas e mosquitos da espécie Stegomyia albopicta foram utilizados para a identificação da transmissão vertical do vírus dengue na natureza e para confirmar a capacidade vetorial em relação à infecção pelo DENV-2 infection. A taxa mínima de infecção em relação à infecção do S. albopicta com o Dengue virus foi de 1:36,45. No Brasil, esta é a primeira vez que altas taxas de infecção mínima da transmissão vertical de S. albopicta foram detectadas nessa espécie.Palavras-chave: Dengue vírus, transmissão vertical, Stegomyia albopicta, capacidade vetorial.