scholarly journals Engineered resistance to Zika virus in transgenic Ae. aegypti expressing a polycistronic cluster of synthetic miRNAs

2018 ◽  
Author(s):  
Anna Buchman ◽  
Stephanie Gamez ◽  
Ming Li ◽  
Igor Antoshechkin ◽  
Shin-Hang Lee ◽  
...  

AbstractRecent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered microRNAs (miRNAs) targeting ZIKV is expressed and fully processed following a blood meal in Ae. aegypti, ensuring the formation of mature synthetic miRNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.One Sentence SummaryHere we describe the generation of Ae. aegypti mosquitoes that are engineered to confer reduced vector competence to Zika virus (ZIKV) and we discuss how such engineering approach can be used to combat the major health burden of ZIKV and potentially other arboviruses in the future.

2019 ◽  
Vol 116 (9) ◽  
pp. 3656-3661 ◽  
Author(s):  
Anna Buchman ◽  
Stephanie Gamez ◽  
Ming Li ◽  
Igor Antoshechkin ◽  
Hsing-Han Li ◽  
...  

Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive-based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered synthetic small RNAs targeting ZIKV is expressed and fully processed in Aedes aegypti, ensuring the formation of mature synthetic small RNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.


Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1345
Author(s):  
Rosilainy Surubi Fernandes ◽  
Mariana Rocha David ◽  
Filipe Vieira Santos De Abreu ◽  
Anielly Ferreira-de-Brito ◽  
Noemi R. Gardinali ◽  
...  

Despite worldwide efforts to understand the transmission dynamics of Zika virus (ZIKV), scanty evaluation has been made on the vector competence of Aedes aegypti fed directly on viremic human and non-human primates (NHPs). We blood-fed Ae. aegypti from two districts in Rio de Janeiro on six ZIKV infected pregnant rhesus macaques at several time points, half of which were treated with Sofosbuvir (SOF). Mosquitoes were analyzed for vector competence after 3, 7 and 14 days of incubation. Although viremia extended up to eight days post monkey inoculation, only mosquitoes fed on the day of the peak of viremia, recorded on day two, became infected. The influence of SOF treatment could not be assessed because the drug was administered just after mosquito feeding on day two. The global infection, dissemination and transmission rates were quite low (4.09%, 1.91% and 0.54%, respectively); no mosquito was infected when viremia was below 1.26 × 105 RNA copies/mL. In conclusion, Ae. aegypti vector competence for ZIKV from macaques is low, likely to be due to low viral load and the short duration of ZIKV viremia in primates suitable for infecting susceptible mosquitoes. If ZIKV infection in human and macaques behaves similarly, transmission of the Zika virus in nature is most strongly affected by vector density.


2017 ◽  
Vol 22 (2) ◽  
Author(s):  
Anna Heitmann ◽  
Stephanie Jansen ◽  
Renke Lühken ◽  
Mayke Leggewie ◽  
Marlis Badusche ◽  
...  

Mosquitoes collected in Germany in 2016, including Culex pipiens pipiens biotype pipiens, Culex torrentium and Aedes albopictus, as well as Culex pipiens pipiens biotype molestus (in colony since 2011) were experimentally infected with Zika virus (ZIKV) at 18 °C or 27 °C. None of the Culex taxa showed vector competence for ZIKV. In contrast, Aedes albopictus were susceptible for ZIKV but only at 27 °C, with transmission rates similar to an Aedes aegypti laboratory colony tested in parallel.


Author(s):  
Rebecca A Zimler ◽  
Donald A Yee ◽  
Barry W Alto

Abstract Recurrence of local transmission of Zika virus in Puerto Rico is a major public health risk to the United States, where mosquitoes Aedes aegypti (Linnaeus) and Aedes mediovittatus (Coquillett) are abundant. To determine the extent to which Ae. mediovittatus are capable of transmitting Zika virus and the influence of viremia, we evaluated infection and transmission in Ae. mediovittatus and Ae. aegypti from Puerto Rico using serial dilutions of infectious blood. Higher doses of infectious blood resulted in greater infection rates in both mosquitoes. Aedes aegypti females were up to twice as susceptible to infection than Ae. mediovittatus, indicating a more effective midgut infection barrier in the latter mosquito species. Aedes aegypti exhibited higher disseminated infection (40–95%) than Ae. mediovittatus (<5%), suggesting a substantial midgut escape barrier in Ae. mediovittatus. For Ae. aegypti, transmission rates were low over a range of doses of Zika virus ingested, suggesting substantial salivary gland barriers.


Insects ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 592
Author(s):  
Valentina Candian ◽  
Monia Monti ◽  
Rosemarie Tedeschi

The transmission of phytoplasmas is the result of an intricate interplay involving pathogens, insect vectors and host plants. Knowledge of the vector’s competence during its lifespan allows us to define more sustainable well-timed control strategies targeted towards the most worrisome life stages. We investigated the temporal dynamics of ‘Candidatus Phytoplasma mali’ load in Cacopsylla melanoneura in the different developmental stages in Northwest Italy. The phytoplasma load in the vector was evaluated in overwintering adults, nymphs and newly emerged adults after different acquisition access periods. Moreover, we followed the multiplication of the phytoplasma during the aestivation and the overwintering period on conifers. Our results confirmed the ability of remigrants to retain the phytoplasma until the end of winter. We also highlighted the high acquisition efficiency and vector competence, based on phytoplasma load, of nymphs and newly emerged adults. Therefore, particular attention should be paid to the management of overwintered C. melanoneura as soon as they return to the orchards, but also to newly emerged adults, particularly in orchards with a high infection rate and when the migration to conifers is delayed.


2017 ◽  
Vol 6 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Chun-xiao Li ◽  
Xiao-xia Guo ◽  
Yong-qiang Deng ◽  
Dan Xing ◽  
Ai-juan Sun ◽  
...  

Insects ◽  
2018 ◽  
Vol 9 (4) ◽  
pp. 177 ◽  
Author(s):  
Tereza Magalhaes ◽  
Alexis Robison ◽  
Michael Young ◽  
William Black ◽  
Brian Foy ◽  
...  

In urban settings, chikungunya, Zika, and dengue viruses are transmitted by Aedes aegypti mosquitoes. Since these viruses co-circulate in several regions, coinfection in humans and vectors may occur, and human coinfections have been frequently reported. Yet, little is known about the molecular aspects of virus interactions within hosts and how they contribute to arbovirus transmission dynamics. We have previously shown that Aedes aegypti exposed to chikungunya and Zika viruses in the same blood meal can become coinfected and transmit both viruses simultaneously. However, mosquitoes may also become coinfected by multiple, sequential feeds on single infected hosts. Therefore, we tested whether sequential infection with chikungunya and Zika viruses impacts mosquito vector competence. We exposed Ae. aegypti mosquitoes first to one virus and 7 days later to the other virus and compared infection, dissemination, and transmission rates between sequentially and single infected groups. We found that coinfection rates were high after sequential exposure and that mosquitoes were able to co-transmit both viruses. Surprisingly, chikungunya virus coinfection enhanced Zika virus transmission 7 days after the second blood meal. Our data demonstrate heterologous arbovirus synergism within mosquitoes, by unknown mechanisms, leading to enhancement of transmission under certain conditions.


2016 ◽  
Vol 10 (9) ◽  
pp. e0005024 ◽  
Author(s):  
Vaea Richard ◽  
Tuterarii Paoaafaite ◽  
Van-Mai Cao-Lormeau

2019 ◽  
Author(s):  
Shivanand Hegde ◽  
Denis Voronin ◽  
Aitor Casas-Sanchez ◽  
Miguel A. Saldaña ◽  
Eva Heinz ◽  
...  

AbstractMicrobiota within mosquitoes influence nutrition, immunity, fecundity, and the capacity to transmit pathogens. Despite their importance, we have a limited understanding of host-microbiota interactions, especially at the cellular level. It is evident bacterial symbionts that are localized within the midgut also infect other organs within the mosquito; however, the route these symbionts take to colonize other tissues is unknown. Here, utilizing the gentamicin protection assay, we showed that the bacterial symbionts Cedecea and Serratia have the capacity to invade and reside intracellularly within mosquito cells. Symbiotic bacteria were found within a vacuole and bacterial replication was observed in mosquito cell by transmission electron microscopy, indicating bacteria were adapted to the intracellular milieu. Using gene silencing, we determined that bacteria exploited host factors, including actin and integrin receptors, to actively invade mosquito cells. As microbiota can affect pathogens within mosquitoes, we examined the influence of intracellular symbionts on Zika virus (ZIKV) infection. Mosquito cells harbouring intracellular bacteria had significantly less ZIKV compared to uninfected cells or cells exposed to non-invasive bacteria. Intracellular bacteria were observed to substantially upregulate the Toll and IMD innate immune pathways, providing a possible mechanism mediating these anti-viral effects. Examining mono-axenically infected mosquitoes using transmission electron and fluorescent microscopy revealed that bacteria occupied an intracellular niche in vivo. Our results provided evidence that bacteria that associate with the midgut of mosquitoes have intracellular lifestyles which likely have implications for mosquito biology and pathogen infection. This study expands our understanding of host-microbiota interactions in mosquitoes, which is important as symbiont microbes are being exploited for vector control strategies.


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