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Cruz, O. G.

Publications and source records attributed to Cruz, O. G..

3 recordsLinked to original sources

A cytochrome P450 G subfamily member, CYP4G35, is highly expressed in antennae and modulates olfactory response in Aedes aegypti mosquitoes.

The cytochrome P450 enzymes of the CYP4G subfamily are some of the most enigmatic insect P450s. The dipterans with sequenced genomes have two CYP4G paralogs. In Drosophila melanogaster, CYP4G1 is highly expressed in the oenocytes and catalyzes the last enzymatic step in the biosynthesis of cuticular hydrocarbons. In contrast, CYP4G15 is expressed in the brain glial cells, but its function is unknown. The Aedes aegypti genome encodes two CYP4Gs: CYP4G36 (ortholog of DmCYP4G1) and CYP4G35 (ortholog of DmCYP4G15). Here, we show that CYP4G35 is highly expressed in mosquito antennae, and the RNAi knockdown of CYP4G35 results in delayed host-seeking. Ae. aegypti CYP4G knockout lines confirmed delayed host-seeking behavior in CYP4G35 knockout females. Proteomics analysis of CYP4G35 KO females also corroborates the physiological findings and shows upregulation of proteins related to olfaction and other CYP4Gs to compensate for the lack of CYP4G35. Immunohistochemistry and in situ hybridization were used to localize CYP4G35 and demonstrated its expression in the sensilla lymph of the antennae and the tip of the proboscis. CYP4G35 and CYP4G36 fusion proteins with cytochrome P450 reductase demonstrated that, unlike CYP4G36, CYP4G35 lacks an oxidative decarbonylase function. Together, our data support a novel function of CYP4G35 in modulating olfactory response.

molecular biology↗

Wolbachia introgression in Rio de Janeiro remains at sub-optimal levels 30 months after its crash: challenges in the sustainability of wMel interventions for dengue control

The deployment of the Wolbachia wMel strain is currently underway in multiple dengue-endemic municipalities across Brazil. The efficacy of this strategy in Rio de Janeiro remains uncertain, primarily due to the difficulty in sustaining high wMel prevalence in regions previously subjected to large-scale releases. A key contributing factor was the routine rotation of insecticides within the framework of Integrated Vector Management (IVM), which led to the use of the larvicide Spinosad for Aedes control in urban areas. This compound was associated with a precipitous decline in Aedes aegypti mosquitoes, regardless the wMel infection status. While wMel-uninfected population recovered within weeks, wMel-infected population remained at low levels likely due to the fitness costs imposed by wMel on egg viability. To assess the long-term persistence of wMel following this demographic collapse, we conducted mosquito sampling across 12 neighborhoods in Rio de Janeiro, 30 months after mosquito populations crashed. Our findings reveal that wMel introgression remains suboptimal, with a mean frequency of 9.87% across the sampled areas. Only two neighborhoods exhibited wMel frequencies exceeding 15%, likely reflecting ongoing localized releases. The reduced prevalence underscores the challenges of achieving self-sustaining wMel establishment in complex urban environments and highlight critical considerations for the implementation of Wolbachia-based dengue control programs in endemic regions. SponsorshipThis study was supported by grants from the CNPq - Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (312282/2022-2, 307209/2023-7) and by FAPERJ - Fundacao Carlos Chagas Filho de Amparo a Pesquisa no Estado do Rio de Janeiro (E-26/211.159/2019, E-26/204.108/2024, E26/2001.844/2017, E-26/210.335/2022, E-26/210.537/2024).

ecology↗

Space-time clusters of dengue, chikungunya, and Zika cases in the city of Rio de Janeiro

Brazil is a dengue-endemic country where all four dengue virus serotypes circulate and cause seasonal epidemics. Recently, chikungunya and Zika viruses were also introduced. In Rio de Janeiro city, the three diseases co-circulated for the first time in 2015-2016, resulting in what is known as the triple epidemic. In this study, we identify space-time clusters of dengue, chikungunya, and Zika, to understand the dynamics and interaction between these simultaneously circulating arboviruses in a densely populated and heterogeneous city.\n\nWe conducted a spatio-temporal analysis of weekly notified cases of the three diseases in Rio de Janeiro city (July 2015 - January 2017), georeferenced by 160 neighbourhoods, using Kulldorffs scan statistic with discrete Poisson probability models.\n\nThere were 26549, 13662, and 35905 notified cases of dengue, chikungunya, and Zika, respectively. The 17 dengue clusters and 15 Zika clusters were spread all over the city, while the 14 chikungunya clusters were more concentrated in the North and Downtown areas. Zika clusters persisted over a longer period of time. The multivariate scan statistic - used to analyse the three diseases simultaneously - detected 17 clusters, nine of which included all three diseases.\n\nThis is the first study exploring space-time clustering of dengue, chikungunya, and Zika in an intraurban area. In general, the clusters did not coincide in time and space. This is probably the result of the competition between viruses for host resources, and of vector-control attitudes promoted by previous arbovirus outbreaks. The main affected area - the North region - is characterised by a combination of high population density and low human development index, highlighting the importance of targeting interventions in this area. Spatio-temporal scan statistics have the potential to direct interventions to high-risk locations in a timely manner and should be considered as part of the municipal surveillance routine as a tool to optimize prevention strategies.\n\nAuthor summaryDengue, an arboviral disease transmitted by Aedes mosquitoes, has been endemic in Brazil for decades, but vector-control strategies have not led to a significant reduction in the disease burden and were not sufficient to prevent chikungunya and Zika entry and establishment in the country. In Rio de Janeiro city, the first Zika and chikungunya epidemics were detected between 2015-2016, coinciding with a dengue epidemic. Understanding the behaviour of these diseases in a triple epidemic scenario is a necessary step for devising better interventions for prevention and outbreak response. We applied scan statistics analysis to detect spatio-temporal clustering for each disease separately and for all three simultaneously. In general, clusters were not detected in the same locations and time periods, possibly due to competition between viruses for host resources, and change in behaviour of the human population (e.g. intensified vector-control activities in response to increasing cases of a particular arbovirus). Neighbourhoods with high population density and social vulnerability should be considered as important targets for interventions. Particularly in the North region, where clusters of the three diseases exist and the first chikungunya cluster occurred. The use of space-time cluster detection can direct intensive interventions to high-risk locations in a timely manner.

epidemiology↗