scholarly journals Development of miRNA-Based Approaches to Explore the Interruption of Mosquito-Borne Disease Transmission

Author(s):  
Tie-Long Xu ◽  
Ya-Wen Sun ◽  
Xin-Yu Feng ◽  
Xiao-Nong Zhou ◽  
Bin Zheng

MicroRNA (miRNA or miR)-based approaches to interrupt the transmission of mosquito-borne diseases have been explored since 2005. A review of these studies and areas in which to proceed is needed. In this review, significant progress is reviewed at the level of individual miRNAs, and miRNA diversification and relevant confounders are described in detail. Current miRNA studies in mosquitoes include four steps, namely, identifying miRNAs, validating miRNA-pathogen interactions, exploring action mechanisms, and performing preapplication investigations. Notably, regarding the Plasmodium parasite, mosquito miRNAs generally bind to mosquito immunity- or development-related mRNAs, indirectly regulating Plasmodium infection; However, regarding arboviruses, mosquito miRNAs can bind to the viral genome, directly modifying viral replication. Thus, during explorations of miRNA-based approaches, researchers need select an ideal miRNA for investigation based on the mosquito species, tissue, and mosquito-borne pathogen of interest. Additionally, strategies for miRNA-based approaches differ for arboviruses and protozoan parasites.

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Eiichiro Kawai ◽  
Seiichi Omura ◽  
Fumitaka Sato ◽  
Nicholas E Martinez ◽  
Viromi Fernando ◽  
...  

Viral myocarditis has been proposed to be initiated by viral replication in the heart (acute phase), followed by immune-mediated damage (subacute phase), where each phase requires anti-viral and immunomodulatory treatments, respectively. There are no specific biomarkers to distinguish acute from subacute phases of myocarditis while serum troponin, echocardiography, and myocardial biopsy data have been used for diagnosis clinically. To determine the phase-specific biomarkers, we used a mouse model for myocarditis induced by Theiler’s murine encephalomyelitis virus (TMEV), which belongs to the genus Cardiovirus, the family Picornaviridae. We conducted multivariate analyses of viral genome, serum cardiac troponin I, echocardiography, histology, and transcriptome using microarray data of the heart tissue harvested on 4 (acute) and 7 (subacute) days post infection (dpi). The level of viral RNA semi-quantified by RT-PCR was 10-fold higher on 4 dpi (ΔCt = 2.5×10-2 ± 4.9×10-3) than 7 dpi (ΔCt = 2.6×10-3 ± 3.0×10-4) (P < 0.05). Serum troponin was undetectable in 4 of 10 mice on 4 dpi and only in 1 of 10 mice on 7 dpi; the serum troponin levels (ng/ml) on 4 dpi (42.9 ± 15.6) were significantly lower than 7 dpi (249.9 ± 62.8) (P < 0.05). The levels of viral RNA and troponin were strongly correlated on 4 dpi (r = 0.79, P < 0.05), but not 7 dpi (P = 0.12), suggesting that viral replication could be a major cause of myocardial damage only on 4 dpi. We found multiple high intensity cardiac lesions using echocardiography with histological myocarditis on 7 dpi, but not 4 dpi. Transcriptome analyses of microarray data showed upregulation of genes associated with innate immune responses in samples from 4 and 7 dpi, compared with controls. Samples from 7 dpi showed upregulation of genes associated with T, B, and antigen presenting cells and downregulation of cardiac myosin-related genes (Myl4, Myl7, and Mybphl), compared with 4 dpi, suggesting that acquired immune responses contribute to cardiomyocyte damage on 7 dpi. In summary, the chronological order of emergence of biomarker candidates was 1) viral genome and innate immunity, 2) troponin, and 3) acquired immunity and echo and histological changes.


Insects ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 269
Author(s):  
Eleanor N. Field ◽  
Ryan E. Tokarz ◽  
Ryan C. Smith

The ecology and environmental conditions of a habitat have profound influences on mosquito population abundance. As a result, mosquito species vary in their associations with particular habitat types, yet long-term studies showing how mosquito populations shift in a changing ecological landscape are lacking. To better understand how land use changes influence mosquito populations, we examined mosquito surveillance data over a thirty-four-year period for two contrasting sites in central Iowa. One site displayed increasing levels of urbanization over time and a dramatic decline in Culex pipiens group (an informal grouping of Culex restuans, Culex pipiens, and Culex salinarius, referred to as CPG), the primary vectors of West Nile virus in central Iowa. Similar effects were also shown for other mosquito vector populations, yet the abundance of Aedes vexans remained constant during the study period. This is in contrast to a second site, which reflected an established urban landscape. At this location, there were no significant changes in land use and CPG populations remained constant. Climate data (temperature, total precipitation) were compiled for each location to see if these changes could account for altered population dynamics, but neither significantly influence CPG abundance at the respective site locations. Taken together, our data suggest that increased landscape development can have negative impacts on Culex vector populations, and we argue that long-term surveillance paired with satellite imagery analysis are useful methods for measuring the impacts of rapid human development on mosquito vector communities. As a result, we believe that land use changes can have important implications for mosquito management practices, population modeling, and disease transmission dynamics.


2020 ◽  
Author(s):  
Matthew J. Valentine ◽  
Brenda Ciraola ◽  
Gregory R. Jacobs ◽  
Charlie Arnot ◽  
Patrick J. Kelly ◽  
...  

AbstractBackgroundHigh quality mosquito surveys that collect fine resolution local data on mosquito species’ abundances provide baseline data to help us understand potential host-pathogen-mosquito relationships, accurately predict disease transmission, and target mosquito control efforts in areas at risk of mosquito borne diseases.MethodsAs part of an investigation into arboviral sylvatic cycles on the Caribbean island of St. Kitts, we carried out an island wide mosquito survey from November 2017 to March 2019. Using Biogents Sentinel 2 and miniature CDC light traps that were set monthly and run for 48 hour intervals, we collected mosquitoes from a total of 30 sites distributed across the five common land covers on the island (agricultural, mangrove, rainforest, scrub, and urban). We developed a mixed effects negative binomial regression model to predict the effects of land cover, seasonality, and precipitation on observed counts of the most abundant mosquito species we found.ResultsWe captured 10 of the 14 mosquito species reported on the island, the four most abundant being Aedes taeniorhynchus, Culex quinquefasciatus, Aedes aegpyti, and Deinocerites magnus. Sampling in the mangroves yielded the most mosquitoes, with Ae. taeniorhynchus, Cx. quinquefasciatus, and De. magnus predominating. Aedes aegypti was recovered primarily from urban and agricultural habitats, but also at lower frequency in other land covers. Psorophora pygmaea and Toxorhynchites guadeloupensis were only captured in scrub habitat. Capture rates in rainforests were low. Our models indicated the relative abundance of the four most common species varied seasonally and with land cover. They also suggested that the extent to which monthly average precipitation influenced counts varied according to species.ConclusionsThis study demonstrates there is high seasonality in mosquito abundances and that land cover influenced the distribution and abundance of mosquito species on St. Kitts. Further, human-adapted mosquito species (e.g. Ae. aegypti and Cx. quinquefasciatus) that are known vectors for many human relevant pathogens are the most wide-spread (across land covers) and the least responsive to seasonal variation in precipitation.


2021 ◽  
Vol 3 (1) ◽  
pp. 1-12
Author(s):  
Muhammad Mikail Athif Zhafir Asyura ◽  
Ahmad Fauzi ◽  
Fakhru Adlan Ayub

Introduction: Dengue Virus (DENV) is the pathogen for human dengue fever and is responsible for 390 million infections per year. The viral genome produces about 10 viral protein products, one of them being NS1. The NS1 protein plays a key role in viral replication and stimulation of humoral immune cells, thus being the perfect candidate to create an effective antiviral drug or vaccine for dengue Methods: Dengue Virus (DENV) is the pathogen for human dengue fever and is responsible for 390 million infections per year. The viral genome produces about 10 viral protein products, one of them being NS1. The NS1 protein plays a key role in viral replication and stimulation of humoral immune cells, thus being the perfect candidate to create an effective antiviral drug or vaccine for dengue Conclusion: The review established promising results of using peptide-based intervention on NS1. Further in vivo and randomized controlled trials are advised to solidify the applicability and biosafety of the intervention    


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Meredith R. Spence Beaulieu ◽  
Jennifer L. Federico ◽  
Michael H. Reiskind

Abstract Background Urbanization is occurring rapidly on a global scale and is altering mosquito communities, creating assemblages that are characteristically less diverse. Despite high rates of urbanization and ample examples of vector-borne diseases transmitted by multiple species, the effects of urbanization-driven mosquito diversity losses on disease transmission has not been well explored. We investigated this question using the dog heartworm, a filarial parasite vectored by numerous mosquito species. Methods We trapped host-seeking mosquitoes in undeveloped areas and neighborhoods of different ages in Wake County, North Carolina, USA, analyzing captured mosquitoes for heartworm DNA. We compared within-mosquito heartworm infection across land-use types by Kruskal–Wallis and likelihood ratio tests. Using zip code level data acquired from dogs in a local shelter, we performed linear regressions of within-host heartworm prevalence by within-mosquito heartworm prevalence as well as by three mosquito diversity measures. We also determined the best predictor of host-level prevalence among models including within-mosquito infection, mosquito diversity and abundance, and socioeconomic status as variables. Results Suburban areas had lower within-mosquito heartworm prevalence and lower likelihood of heartworm-positive mosquitoes than did undeveloped field sites, although no differences were seen between suburban and undeveloped wooded sites. No relationships were noted between within-mosquito and within-host heartworm prevalence. However, mosquito diversity metrics were positively correlated with host heartworm prevalence. Model selection revealed within-host prevalence was best predicted by a positive relationship with mosquito Shannon–Wiener diversity and a negative relationship with household income. Conclusions Our results demonstrate that decreases in mosquito diversity due to urbanization alter vector-borne disease risk. With regard to dog heartworm disease, this loss of mosquito diversity is associated with decreased heartworm prevalence within both the vector and the host. Although the response is likely different for diseases transmitted by one or few species, mosquito diversity losses leading to decreased transmission could be generalizable to other pathogens with multiple vectors. This study contributes to better understanding of the effects of urbanization and the role of vector diversity in multi-vectored pathosystems.


2004 ◽  
Vol 78 (22) ◽  
pp. 12480-12488 ◽  
Author(s):  
Mark Trottier ◽  
Brian P. Schlitt ◽  
Aisha Y. Kung ◽  
Howard L. Lipton

ABSTRACT The dynamics of Theiler's murine encephalomyelitis virus (TMEV) RNA replication in the central nervous systems of susceptible and resistant strains of mice were examined by quantitative real-time reverse transcription-PCR and were found to correlate with host immune responses. During the acute phase of infection in both susceptible and resistant mice, levels of viral replication were high in the brain and brain stem, while levels of viral genome equivalents were 10- to 100-fold lower in the spinal cord. In the brain, viral RNA replication decreased after a peak at 5 days postinfection (p.i.), in parallel with the appearance of virus-specific antibody responses; however, by 15 days p.i., viral RNA levels began to increase in the spinal cords of susceptible mice. During the transition to and the persistent phase of infection, the numbers of viral genome equivalents in the spinal cord varied substantially for individual mice, but high levels were consistently associated with high levels of proinflammatory Th1 cytokine and chemokine mRNAs. Moreover, a large number of viral genome equivalents and high proinflammatory cytokine mRNA levels in spinal cords were only observed for susceptible SJL/J mice who developed demyelinating disease. These results suggest that TMEV persistence requires active viral replication beginning about day 11 p.i. and that active viral replication with high viral genome loads leads to increased levels of Th1 cytokines that drive disease progression in infected mice.


2016 ◽  
Vol 90 (16) ◽  
pp. 7285-7302 ◽  
Author(s):  
Kara Jensen ◽  
Rafiq Nabi ◽  
Koen K. A. Van Rompay ◽  
Spencer Robichaux ◽  
Jeffrey D. Lifson ◽  
...  

ABSTRACTDespite significant progress in reducing peripartum mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) with antiretroviral therapy (ART), continued access to ART throughout the breastfeeding period is still a limiting factor, and breast milk exposure to HIV accounts for up to 44% of MTCT. As abstinence from breastfeeding is not recommended, alternative means are needed to prevent MTCT of HIV. We have previously shown that oral vaccination at birth with live attenuatedMycobacterium tuberculosisstrains expressing simian immunodeficiency virus (SIV) genes safely induces persistent SIV-specific cellular and humoral immune responses both systemically and at the oral and intestinal mucosa. Here, we tested the ability of oralM. tuberculosisvaccine strains expressing SIV Env and Gag proteins, followed by systemic heterologous (MVA-SIV Env/Gag/Pol) boosting, to protect neonatal macaques against oral SIV challenge. While vaccination did not protect infant macaques against oral SIV acquisition, a subset of immunized animals had significantly lower peak viremia which inversely correlated with prechallenge SIV Env-specific salivary and intestinal IgA responses and higher-avidity SIV Env-specific IgG in plasma. These controller animals also maintained CD4+T cell populations better and showed reduced tissue pathology compared to noncontroller animals. We show that infants vaccinated at birth can develop vaccine-induced SIV-specific IgA and IgG antibodies and cellular immune responses within weeks of life. Our data further suggest that affinity maturation of vaccine-induced plasma antibodies and induction of mucosal IgA responses at potential SIV entry sites are associated with better control of viral replication, thereby likely reducing SIV morbidity.IMPORTANCEDespite significant progress in reducing peripartum MTCT of HIV with ART, continued access to ART throughout the breastfeeding period is still a limiting factor. Breast milk exposure to HIV accounts for up to 44% of MTCT. Alternative measures, in addition to ART, are needed to achieve the goal of an AIDS-free generation. Pediatric HIV vaccines constitute a core component of such efforts. The results of our pediatric vaccine study highlight the potential importance of vaccine-elicited mucosal Env-specific IgA responses in combination with high-avidity systemic Env-specific IgG in protection against oral SIV transmission and control of viral replication in infant macaques. The induction of potent mucosal IgA antibodies by our vaccine is remarkable considering the age-dependent development of mucosal IgA responses postbirth. A deeper understanding of postnatal immune development may inform the design of improved vaccine strategies to enhance systemic and mucosal SIV/HIV antibody responses.


2019 ◽  
Vol 24 (5) ◽  
Author(s):  
Shinji Kasai ◽  
Beniamino Caputo ◽  
Takashi Tsunoda ◽  
Tran Chi Cuong ◽  
Yoshihide Maekawa ◽  
...  

Introduction Aedes albopictus (Skuse) is an important vector of arboviral diseases, including dengue, chikungunya and Zika virus disease. Monitoring insecticide resistance and mechanisms by which the mosquito develops resistance is crucial to minimise disease transmission. Aim To determine insecticide resistance status and mechanisms in Ae. albopictus from different geographical regions. Methods We sampled 33 populations of Ae. albopictus from Asia, Europe and South America, and tested these for susceptibility to permethrin, a pyrethroid insecticide. In resistant populations, the target site for pyrethroids, a voltage-sensitive sodium channel (Vssc) was genotyped. Three resistant sub-strains, each harbouring a resistance allele homozygously, were established and susceptibilities to three different pyrethroids (with and without a cytochrome P450 inhibitor) were assayed. Results Most populations of Ae. albopictus tested were highly susceptible to permethrin but a few from Italy and Vietnam (4/33), exhibited high-level resistance. Genotyping studies detected a knockdown resistance (kdr) allele V1016G in Vssc for the first time in Ae. albopictus. Two previously reported kdr alleles, F1534C and F1534S, were also detected. The bioassays indicated that the strain homozygous for the V1016G allele showed much greater levels of pyrethroid resistance than other strains harbouring F1534C or F1534S. Conclusion The V1016G allele was detected in both Asian and Italian Ae. albopictus populations, thus a spread of this allele beyond Italy in Europe cannot be ruled out. This study emphasises the necessity to frequently and regularly monitor the V1016G allele in Ae. albopictus, particularly where this mosquito species is the main vector of arboviruses.


2020 ◽  
Vol 57 (6) ◽  
pp. 1913-1919
Author(s):  
Walter Santos de Araújo ◽  
Thallyta Maria Vieira ◽  
Guilherme Antunes de Souza ◽  
Isaque Clementino Bezerra ◽  
Paulo Henrique Costa Corgosinho ◽  
...  

Abstract Mosquitoes (Diptera: Culicidae) are one of the most important disease vector species in the world. Many species have a high degree of anthropophilia and are often found in human habitations. In the present study, we have inventoried the nocturnal mosquito assemblage in intra-, peri-, and extradomicile environments in four municipalities in Pará, Brazil. At each municipality, a residence was selected and the mosquitoes were sampled using the protected human attraction capture and Shannon trap methods in April (rainy season) and August 2018 (dry season). We have collected a total of 696 mosquito specimens belonging to 8 genera and 17 species. The most abundant species were Mansonia (Mansonoides) titillans (Walker) (366/696, 52.6%), Anopheles (Nyssorhynchus) albitarsis Lynch-Arribálzaga (97/696, 13.9%), and Culex (Culex) quinquefasciatus Say (93/696, 13.4%). Mosquito richness, abundance, and composition did not differ between intra-, peri-, and extradomicile environments suggesting limited habitat segregation among the different species. However, mosquito species richness and mosquito species abundance were significantly higher during the rainy season than during the dry season, suggesting increased mosquito activity during the rainy season. We detected several important vector species of human diseases including Aedes (Stegomyia) aegypti (Linnaeus), Anopheles (Nyssorhynchus) darlingi Root, Haemagogus (Conopostegus) leucocelaenus (Dyar and Shannon), Coquillettidia (Coquillettidia) venezuelensis (Theobald), and Culex (Culex) quinquefasciatus which are the main transmitters of dengue, malaria, yellow fever, mayaro, and oropouche fever, respectively. As inventories of disease-carrying mosquitoes in the region are very scarce, mainly in residential environments, our results suggest high potential for mosquito-borne disease transmission in Pará State.


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