scholarly journals Wolbachia strain wAu differs in cellular perturbation and virus inhibition profiles from previously characterised Wolbachia strains

2021 ◽  
Author(s):  
Stephanie Rainey ◽  
Vincent Geoghegan ◽  
Daniella Lefteri ◽  
Thomas Ant ◽  
Julien Martinez ◽  
...  

Some strains of the inherited bacterium Wolbachia have been shown to be effective at reducing the transmission of dengue and other positive-sense RNA viruses by Aedes aegypti in both laboratory and field settings and are being deployed for dengue control. The degree of virus inhibition varies between Wolbachia strains density and tissue tropism can contribute to these differences but there are also indications that this is not the only factor involved: for example, strains wAu and wAlbA are maintained at similar densities but only wAu produces strong dengue inhibition. We previously reported perturbations in lipid transport dynamics, including sequestration of cholesterol in lipid droplets, with strains wMel/wMelPop in Ae.aegypti. Here we show that strain wAu does not produce the same cholesterol sequestration phenotype despite displaying strong virus inhibition and moreover, in contrast to wMel, wAu antiviral activity was not rescued by cyclodextrin treatment. To further investigate the cellular basis underlying these differences, proteomic analysis of midguts was carried out on Ae. aegypti lines and revealed that wAu-carrying midguts showed a distinct proteome when compared to Wolbachia-free, wMel- or wAlbA-carrying midguts, in particular with respect to lipid transport and metabolism. The data suggest a possible role for perturbed RNA processing pathways in wAu virus inhibition. Together these results indicate that wAu shows unique features in its inhibition of arboviruses compared to previously characterized Wolbachia strains.

2013 ◽  
Vol 2013 ◽  
pp. 1-21 ◽  
Author(s):  
Giuseppe Sautto ◽  
Nicasio Mancini ◽  
Giacomo Gorini ◽  
Massimo Clementi ◽  
Roberto Burioni

More than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. Effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. On the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particular for emergency cases. Neutralizing monoclonal antibodies (mAbs) have been demonstrated to be effective in the treatment of several infectious diseases as well as in preliminaryin vitroandin vivomodels of arbovirus-related infections. Given their specific antiviral activity as well-tolerated molecules with limited side effects, mAbs could represent a new therapeutic approach for the development of an effective treatment, as well as useful tools in the study of the host-virus interplay and in the development of more effective immunogens. However, before their use as candidate therapeutics, possible hurdles (e.g., Ab-dependent enhancement of infection, occurrence of viral escape variants) must be carefully evaluated. In this review are described the main arboviruses infecting humans and candidate mAbs to be possibly used in a future passive immunotherapy.


2018 ◽  
Vol 76 (7) ◽  
pp. 1907-1950 ◽  
Author(s):  
Doris E. Campo-Duarte ◽  
Olga Vasilieva ◽  
Daiver Cardona-Salgado ◽  
Mikhail Svinin

2019 ◽  
Vol 29 (24) ◽  
pp. 4241-4248.e5 ◽  
Author(s):  
Wasi A. Nazni ◽  
Ary A. Hoffmann ◽  
Ahmad NoorAfizah ◽  
Yoon Ling Cheong ◽  
Maria V. Mancini ◽  
...  

2020 ◽  
Vol 16 (7) ◽  
pp. e1008410 ◽  
Author(s):  
Johanna E. Fraser ◽  
Tanya B. O’Donnell ◽  
Johanna M. Duyvestyn ◽  
Scott L. O’Neill ◽  
Cameron P. Simmons ◽  
...  

Author(s):  
Sunaryo Sunaryo ◽  
Dyah Widiastuti

Vector control using insecticide is a major effort to control Dengue Haemorrhagic Fever. The excessive use of insecticides leads to insecticide resistance in Aedes aegypti. This study aimed to determine the resistance status of Aedes aegypti in North Sumatra and Jambi Province to malathion, deltametrin, cypermethrin, lambda cyhalothrin and alpha cypermethrin. A cross sectional study was conducted during 2015, the research location covers North Sumatera area (Tebing Tinggi, Deli Serdang, and Pematang Siantar) and Jambi (Muaro Jambi, Jambi, and Batang Hari). Susceptibility test using WHO kits was applied on F1 generation and interview with Local Public Health Officer was carried out to obtain information about the usage of insecticide in both provinces. Resistance to malathion, cypermethrin, and lambda cyhaltorhin was observed in Ae. aegypti populations from all study area. Tolerant status to deltamethrin only found in Aedes aegypti from Deli Serdang, whilst the other strains were resistant. Ae. aegypti population from all study area were tolerant to alpha cypermethrin. Malathion and cypermethrin were the only insecticide ever used in both provinces. We conclude that alpha cypermethrin was effective to combat Ae. aegypti and can be used as an alternative insecticide for dengue control program in Northern Sumatera and Jambi Province. 


2022 ◽  
Vol 18 (1) ◽  
pp. e1010202
Author(s):  
Rommel J. Gestuveo ◽  
Rhys Parry ◽  
Laura B. Dickson ◽  
Sebastian Lequime ◽  
Vattipally B. Sreenu ◽  
...  

The exogenous small interfering RNA (exo-siRNA) pathway is a key antiviral mechanism in the Aedes aegypti mosquito, a widely distributed vector of human-pathogenic arboviruses. This pathway is induced by virus-derived double-stranded RNAs (dsRNA) that are cleaved by the ribonuclease Dicer 2 (Dcr2) into predominantly 21 nucleotide (nt) virus-derived small interfering RNAs (vsiRNAs). These vsiRNAs are used by the effector protein Argonaute 2 within the RNA-induced silencing complex to cleave target viral RNA. Dcr2 contains several domains crucial for its activities, including helicase and RNase III domains. In Drosophila melanogaster Dcr2, the helicase domain has been associated with binding to dsRNA with blunt-ended termini and a processive siRNA production mechanism, while the platform-PAZ domains bind dsRNA with 3’ overhangs and subsequent distributive siRNA production. Here we analyzed the contributions of the helicase and RNase III domains in Ae. aegypti Dcr2 to antiviral activity and to the exo-siRNA pathway. Conserved amino acids in the helicase and RNase III domains were identified to investigate Dcr2 antiviral activity in an Ae. aegypti-derived Dcr2 knockout cell line by reporter assays and infection with mosquito-borne Semliki Forest virus (Togaviridae, Alphavirus). Functionally relevant amino acids were found to be conserved in haplotype Dcr2 sequences from field-derived Ae. aegypti across different continents. The helicase and RNase III domains were critical for silencing activity and 21 nt vsiRNA production, with RNase III domain activity alone determined to be insufficient for antiviral activity. Analysis of 21 nt vsiRNA sequences (produced by functional Dcr2) to assess the distribution and phasing along the viral genome revealed diverse yet highly consistent vsiRNA pools, with predominantly short or long sequence overlaps including 19 nt overlaps (the latter representing most likely true Dcr2 cleavage products). Combined with the importance of the Dcr2 helicase domain, this suggests that the majority of 21 nt vsiRNAs originate by processive cleavage. This study sheds new light on Ae. aegypti Dcr2 functions and properties in this important arbovirus vector species.


2021 ◽  
Author(s):  
◽  
Lee Ching Ng

Incompatible insect technique (IIT) via releases of male Wolbachia-infected mosquitoes is a promising tool for dengue control. In a three-year trial in Singaporean high-rise housing estates, we demonstrated that Wolbachia-based IIT dramatically reduces both wildtype Aedes aegypti populations [reductions of 92.7% (95% CI: 84.7%-95.8%) and 98.3% (97.7%-99.8%)] and dengue incidence [reductions of 71% (43%-87%) to 88% (57%-99%)] in the targeted areas. The study highlights the need to ensure adequate vertical distribution of released males in high-rise buildings, address immigration of wildtype females from neighboring areas, and prevent and mitigate stable establishment of Wolbachia in field mosquito populations. Our results demonstrate the potential of Wolbachia-based IIT (supplemented with irradiation, in Singapore's context) for strengthening dengue control in tropical cities, where dengue burden is the greatest.


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