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Terradas, G.

Publications and source records attributed to Terradas, G..

6 recordsLinked to original sources

Temperature affects viral kinetics and vectorial capacity of Aedes aegypti mosquitoes co-infected with Mayaro and Dengue viruses

Increasing global temperatures and unpredictable climatic extremes have contributed to the spread of vector-borne diseases. The mosquito Aedes aegypti is the main vector of multiple arboviruses that negatively impact human health, mostly in low socioeconomic areas of the world. Co-circulation and co-infection of these viruses in humans have been increasingly reported; however, how vectors contribute to this alarming trend remains unclear. Here, we examine single and co-infection of Mayaro virus (-D strain, Alphavirus) and dengue virus (serotype 2, Flavivirus) in Ae. aegypti adults and cell lines at two constant temperatures, moderate (27{degrees}C) and hot (32{degrees}C), to quantify vector competence and the effect of temperature on infection, dissemination and transmission, including on the degree of interaction between the two viruses. Both viruses were primarily affected by temperature but there was a partial interaction with co-infection. Dengue virus quickly replicates in adult mosquitoes, with a tendency for higher titers in co-infected mosquitoes at both temperatures and mosquito mortality was more severe at higher temperatures in all conditions. For dengue, and to a lesser extent Mayaro, vector competence and vectorial capacity were higher at hotter temperature in co- vs single infections and was more evident at earlier timepoints (7 vs 14 days post infection). The temperature-dependent phenotype was confirmed in vitro by faster cellular infection and initial replication at higher temperatures for dengue but not for Mayaro virus. Our study suggests that contrasting kinetics of the two viruses could be related to their intrinsic thermal requirements, where alphaviruses thrive better at lower temperatures compared to flaviviruses, but further studies are necessary to clarify the role of co-infection at different and variable temperature regimes. Author summaryGlobal warming is having devastating consequences for the environment, and a cause of concern is the increase in local abundance and geographic range of mosquitoes and the associated viruses they transmit. This study explores how temperature affects the mosquitos ability to survive and potentially spread two viruses, Mayaro and dengue, in single or co-infections. We found that Mayaro virus was not clearly affected by temperature or the presence of dengue infection. In contrast, dengue virus showed higher infection and potential for higher transmission in mosquitoes kept at high temperatures, and this trend was stronger in co-infections compared to single infections. Mosquito survival consistently decreased at high temperatures. We hypothesize the differences observed for dengue virus are due to the faster growth and viral activity in the mosquito at hotter temperatures, a pattern not observed for Mayaro virus. More studies under different temperature regimes are needed to clarify the role of co-infection.

microbiology↗

Dehydration stress and Mayaro virus vector competence in Aedes aegypti

The mosquito Aedes aegypti is a competent vector of multiple pathogens including dengue, Zika, yellow fever, chikungunya, and Mayaro viruses. Ae. aegypti is highly invasive and is currently present in the Americas, Oceania, Asia, and Europe, but its distribution and the pathogens it transmits are expected to change due to climate change. Relative humidity is an environmental variable that affects mosquito biology and distribution and can differ between location, habitat, and season, with mosquitoes facing significant variation in relative humidity during their lifespan. Low relative humidity can induce dehydration in mosquitoes, leading to alterations in physiological and behavioral responses relevant for pathogen transmission such as bloodfeeding and host-seeking behavior. In this study, we evaluated the short and long-term effects of dehydration stress on mortality and Mayaro virus vector competence in Ae. aegypti. Our results show that exposure to dehydration does not impact viral titers, nor infection, dissemination and transmission rates, in mosquitoes infected with Mayaro virus. However, we detected a significant effect of dehydration on mosquito mortality and blood feeding frequency regardless of infection status. The previously observed effects of higher feeding during dehydration and the current observation of altered survival along with no impact on vector competence suggest that the impact of dehydration on viral transmission in mosquitoes will likely be complex.

microbiology↗

Anopheles albimanus is a potential alphavirus vector in the Americas

Despite its ecological flexibility and geographical co-occurrence with human pathogens, little is known about the ability for Anopheles albimanus to transmit arboviruses. To address this gap, we challenged An. albimanus females with four alphaviruses and one flavivirus and monitored progression of infections. We found this species is an efficient vector of the alphaviruses Mayaro virus, Onyong-nyong virus, and Sindbis virus, though the latter two do not currently exist in its habitat range. An. albimanus was able to become infected with Chikungunya virus, but virus dissemination was rare (indicating the presence of a midgut escape barrier), and no mosquito transmitted. Mayaro virus rapidly established disseminated infections in An. albimanus females and was detected in the saliva of a substantial proportion of infected mosquitoes. Consistent with previous work in other anophelines, we find that An. albimanus is refractory to infection with flaviviruses, a phenotype that did not depend on midgut-specific barriers. Our work demonstrates that An. albimanus may be a vector of neglected emerging human pathogens and adds to recent evidence that anophelines are competent vectors for diverse arboviruses.

microbiology↗

Genetic conversion of a split-drive into a full-drive element

Gene-drive systems offer an important new avenue for spreading beneficial traits into wild populations. Their core components, Cas9 and guide RNA (gRNA), can either be linked within a single cassette (full gene drive, fGD) or provided in two separate elements (split gene drive, sGD) wherein the gRNA-bearing element drives in the presence of an independent static source of Cas9. We previously designed a system engineered to turn split into full gene drives. Here, we provide experimental proof-of-principle for such a convertible system inserted at the spo11 locus, which is recoded to restore gene function. In multigenerational cage studies, the reconstituted spo11 fGD cassette initially drives with slower kinetics than the unlinked sGD element (using the same Mendelian vasa-Cas9 source), but eventually reaches a similar level of final introgression. Different kinetic behaviors may result from transient fitness costs associated with individuals co-inheriting Cas9 and gRNA transgenes during the drive process.

genetics↗

Inherently confinable split-drive systems in Drosophila

CRISPR-based gene drive systems, which copy themselves based on gene conversion mediated by the homology directed repair (HDR) pathway, have potential to revolutionize vector control. However, mutant alleles generated by the competing non-homologous end-joining (NHEJ) pathway that are rendered resistant to Cas9 cleavage can interrupt the spread of genedrive elements. We hypothesized that drives targeting genes essential for viability or reproduction also carrying recoded sequences to restore endogenous gene functionality should benefit from dominantly-acting maternal clearance of NHEJ alleles, combined with recessive Mendelian processes. Here, we test split gene-drive (sGD) systems in Drosophila melanogaster that were inserted into essential genes required for viability (rab5, rab11, prosalpha2) or fertility (spo11). In single generation crosses, sGDs copy with variable efficiencies and display sex-biased transmission. In multi-generational cage trials, sGD follow distinct drive trajectories reflecting their differential tendencies to induce target chromosome damage or lethal/sterile mosaic phenotypes, leading to inherently confineable drive outcomes.

genetics↗

Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

The development of Cas9/gRNA-mediated gene-drive systems has bolstered the advancement of genetic technologies for controlling vector-borne pathogen transmission. These include population suppression approaches, genetic analogs of insecticidal techniques that reduce the number of vector insects, and population modification (replacement/alteration) approaches, which interfere with competence to transmit pathogens. We developed a recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and a functional resistant allele does not prevent drive invasion. Small cage trials show that single releases of gene-drive males robustly result in efficient population modification with [≥]95% of mosquitoes carrying the drive within 5-11 generations over a range of initial release ratios.

genetics↗