scholarly journals Dengue virus infection modifies mosquito blood-feeding behavior to increase transmission to the host

2022 ◽  
Vol 119 (3) ◽  
pp. e2117589119
Author(s):  
Benjamin Wong Wei Xiang ◽  
Wilfried A. A. Saron ◽  
James C. Stewart ◽  
Arthur Hain ◽  
Varsha Walvekar ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Denv Infection ◽  
Blood Feeding ◽  
Infected Mosquito ◽  
Transmission Model ◽  
Reproduction Rate ◽  
Behavioral Alterations ◽  
Epidemiological Modeling ◽  
Multidisciplinary Study

Mosquito blood-feeding behavior is a key determinant of the epidemiology of dengue viruses (DENV), the most-prevalent mosquito-borne viruses. However, despite its importance, how DENV infection influences mosquito blood-feeding and, consequently, transmission remains unclear. Here, we developed a high-resolution, video-based assay to observe the blood-feeding behavior of Aedes aegypti mosquitoes on mice. We then applied multivariate analysis on the high-throughput, unbiased data generated from the assay to ordinate behavioral parameters into complex behaviors. We showed that DENV infection increases mosquito attraction to the host and hinders its biting efficiency, the latter resulting in the infected mosquitoes biting more to reach similar blood repletion as uninfected mosquitoes. To examine how increased biting influences DENV transmission to the host, we established an in vivo transmission model with immuno-competent mice and demonstrated that successive short probes result in multiple transmissions. Finally, to determine how DENV-induced alterations of host-seeking and biting behaviors influence dengue epidemiology, we integrated the behavioral data within a mathematical model. We calculated that the number of infected hosts per infected mosquito, as determined by the reproduction rate, tripled when mosquito behavior was influenced by DENV infection. Taken together, this multidisciplinary study details how DENV infection modulates mosquito blood-feeding behavior to increase vector capacity, proportionally aggravating DENV epidemiology. By elucidating the contribution of mosquito behavioral alterations on DENV transmission to the host, these results will inform epidemiological modeling to tailor improved interventions against dengue.

scholarly journals Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination

2020 ◽  
Author(s):  
Alejandro Marin-Lopez ◽  
Junjun Jiang ◽  
Yuchen Wang ◽  
Yongguo Cao ◽  
Tyler MacNeil ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Denv Infection ◽  
Infected Mosquito ◽  
Viral Dissemination ◽  
Protein Components ◽  
Calcium Transporter

AbstractDengue virus (DENV) is a flavivirus that causes marked human morbidity and mortality worldwide, being transmitted to humans by Aedes aegypti mosquitoes. Habitat expansion of Aedes, mainly due to climate change and increasing overlap between urban and wild habitats, places nearly half of the world’s population at risk for DENV infection. After a bloodmeal from a DENV-infected host, the virus enters the mosquito midgut. Next, the virus migrates to, and replicates in, other tissues, like salivary glands. Successful viral transmission occurs when the infected mosquito takes another blood meal on a susceptible host and DENV is released from the salivary gland via saliva into the skin. During viral dissemination in the mosquito and transmission to a new mammalian host, DENV interacts with a variety of vector proteins, which are uniquely important during each phase of the viral cycle. Our study focuses on the interaction between DENV particles and protein components in the A. aegypti vector. We performed a mass spectrometry assay where we identified a set of A aegypti salivary gland proteins which potentially interact with the DENV virion. Using dsRNA to silence gene expression, we analyzed the role of these proteins in viral infectivity. Two of these candidates, a synaptosomal-associated protein (AeSNAP) and a calcium transporter ATPase (ATPase) appear to play a role in viral replication both in vitro and in vivo. These findings suggest that AeSNAP plays a protective role during DENV infection of mosquitoes and that ATPase protein is required for DENV during amplification within the vector.ImportanceAedes aegypti mosquitoes are the major vector of different flaviviruses that cause human diseases, including dengue virus. There is a great need for better therapeutics and preventive vaccines against flaviviruses. Flaviviruses create complex virus-host and virus-vector interactions. The interactions between viral particles and protein components in the vector is not completely understood. In this work we characterize how two mosquito proteins, “AeSNAP” and “ATPase”, influence DENV viral dissemination within A. aegypti, using both in vitro and in vivo models. These results elucidate anti-vector measures that may be potentially be used to control dengue virus spread in the mosquito vector.

scholarly journals Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination

2021 ◽  
Vol 15 (6) ◽  
pp. e0009442
Author(s):  
Alejandro Marin-Lopez ◽  
Junjun Jiang ◽  
Yuchen Wang ◽  
Yongguo Cao ◽  
Tyler MacNeil ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Denv Infection ◽  
Infected Mosquito ◽  
Mammalian Host ◽  
Susceptible Host ◽  
Calcium Transporter

Dengue virus (DENV) is a flavivirus that causes marked human morbidity and mortality worldwide, and is transmitted to humans by Aedes aegypti mosquitoes. Habitat expansion of Aedes, mainly due to climate change and increasing overlap between urban and wild habitats, places nearly half of the world’s population at risk for DENV infection. After a bloodmeal from a DENV-infected host, the virus enters the mosquito midgut. Next, the virus migrates to, and replicates in, other tissues, like salivary glands. Successful viral transmission occurs when the infected mosquito takes another blood meal on a susceptible host and DENV is released from the salivary gland via saliva into the skin. During viral dissemination in the mosquito and transmission to a new mammalian host, DENV interacts with a variety of vector proteins, which are uniquely important during each phase of the viral cycle. Our study focuses on the interaction between DENV particles and protein components in the A. aegypti vector. We performed a mass spectrometry assay where we identified a set of A. aegypti salivary gland proteins which potentially interact with the DENV virion. Using dsRNA to silence gene expression, we analyzed the role of these proteins in viral infectivity. Two of these candidates, a synaptosomal-associated protein (AeSNAP) and a calcium transporter ATPase (ATPase) appear to play a role in viral replication both in vitro and in vivo, observing a ubiquitous expression of these proteins in the mosquito. These findings suggest that AeSNAP plays a protective role during DENV infection of mosquitoes and that ATPase protein is required for DENV during amplification within the vector.

Evaluation of the In Vivo Acute Toxicity and In Vitro Hemolytic and Immunomodulatory Activities of the Moringa oleifera Flower Trypsin Inhibitor (MoFTI)

2020 ◽  
Vol 27 ◽  
Author(s):  
Leydianne Leite de Siqueira Patriota ◽  
Dayane Kelly Dias do Nascimento Santos ◽  
Bárbara Rafaela da Silva Barros ◽  
Lethícia Maria de Souza Aguiar ◽  
Yasmym Araújo Silva ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Trypsin Inhibitor ◽  
Hemolytic Activity ◽  
Moringa Oleifera ◽  
Biological Activities ◽  
Hematological Parameters ◽  
Behavioral Alterations ◽  
Female Mice

Background: Protease inhibitors have been isolated from plants and present several biological activities, including immunomod-ulatory action. Objective: This work aimed to evaluate a Moringa oleifera flower trypsin inhibitor (MoFTI) for acute toxicity in mice, hemolytic activity on mice erythrocytes and immunomodulatory effects on mice splenocytes. Methods: The acute toxicity was evaluated using Swiss female mice that received a single dose of the vehicle control or MoFTI (300 mg/kg, i.p.). Behavioral alterations were observed 15–240 min after administration, and survival, weight gain, and water and food consumption were analyzed daily. Organ weights and hematological parameters were analyzed after 14 days. Hemolytic activity of MoFTI was tested using Swiss female mice erythrocytes. Splenocytes obtained from BALB/c mice were cultured in the absence or presence of MoFTI for the evaluation of cell viability and proliferation. Mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) levels were also determined. Furthermore, the culture supernatants were analyzed for the presence of cytokines and nitric oxide (NO). Results: MoFTI did not cause death or any adverse effects on the mice except for abdominal contortions at 15–30 min after administration. MoFTI did not exhibit a significant hemolytic effect. In addition, MoFTI did not induce apoptosis or necrosis in splenocytes and had no effect on cell proliferation. Increases in cytosolic and mitochondrial ROS release, as well as ΔΨm reduction, were observed in MoFTI-treated cells. MoFTI was observed to induce TNF-α, IFN-γ, IL-6, IL-10, and NO release. Conclusion: These results contribute to the ongoing evaluation of the antitumor potential of MoFTI and its effects on other immunological targets.

scholarly journals EXTH-71. CYTOSTATIC HYPOTHERMIA FOR GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii102-ii103
Author(s):  
Syed Faaiz Enam ◽  
Jianxi Huang ◽  
Cem Kilic ◽  
Connor Tribble ◽  
Martha Betancur ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Progression Free Survival ◽  
Rodent Model ◽  
Behavioral Alterations ◽  
Free Survival ◽  
Tumor Bearing ◽  
Car T ◽  
The Brain

Abstract As a cancer therapy, hypothermia has been used at sub-zero temperatures to cryosurgically ablate tumors. However, these temperatures can indiscriminately damage both tumorous and healthy cells. Additionally, strategies designed to kill tumor typically accelerate their evolution and recurrence can be inevitable in cancers such as glioblastoma (GBM). To bypass these limitations, here we studied the use of hypothermia as a cytostatic tool against cancer and deployed it against an aggressive rodent model of GBM. To identify the minimal dosage of ‘cytostatic hypothermia’, we cultured at least 4 GBM lines at 4 continuous or intermittent degrees of hypothermia and evaluated their growth rates through a custom imaging-based assay. This revealed cell-specific sensitivities to hypothermia. Subsequently, we examined the effects of cytostatic hypothermia on these cells by a cursory study of their cell-cycle, energy metabolism, and protein synthesis. Next, we investigated the use of cytostatic hypothermia as an adjuvant to chemotherapy and CAR T immunotherapy. Our studies demonstrated that cytostatic hypothermia did not interfere with Temozolomide in vitro and may have been synergistic against at least 1 GBM line. Interestingly, we also demonstrated that CAR T immunotherapy can function under cytostatic hypothermia. To assess the efficacy of hypothermia in vivo, we report the design of an implantable device to focally administer cytostatic hypothermia in an aggressive rodent model of F98 GBM. Cytostatic hypothermia significantly doubled the median survival of tumor-bearing rats with no obvious signs of distress. The absence of gross behavioral alterations is in concurrence with literature suggesting the brain is naturally resilient to focal hypothermia. Based on these findings, we anticipate that focally administered cytostatic hypothermia alone has the potential to delay tumor recurrence or increase progression-free survival in patients. Additionally, it could also provide more time to evaluate concomitant, curative cytotoxic treatments.

Beyond Nature and Nurture: Phenotypic Plasticity in Blood-Feeding Behavior of Anopheles gambiae s.s. When Humans Are Not Readily Accessible

2009 ◽  
Vol 81 (6) ◽  
pp. 1023-1029 ◽  
Author(s):  
Thierry Lefèvre ◽  
Frédéric Thomas ◽  
François Renaud ◽  
Eric Elguero ◽  
Didier Fontenille ◽  
...  
Keyword(s):  
Phenotypic Plasticity ◽  
Feeding Behavior ◽  
Anopheles Gambiae ◽  
Blood Feeding ◽  
Anopheles Gambiae S.S ◽  
Nature And Nurture

scholarly journals Comparative sialomics between hard and soft ticks: Implications for the evolution of blood-feeding behavior

2008 ◽  
Vol 38 (1) ◽  
pp. 42-58 ◽  
Author(s):  
Ben J. Mans ◽  
John F. Andersen ◽  
Ivo M.B. Francischetti ◽  
Jesus G. Valenzuela ◽  
Tom G. Schwan ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Blood Feeding

Anti-diuresis in the blood-feeding insect Rhodnius prolixus Stål: the peptide CAP2b and cyclic GMP inhibit Malpighian tubule fluid secretion.

1997 ◽  
Vol 200 (17) ◽  
pp. 2363-2367 ◽  
Author(s):  
M C Quinlan ◽  
N J Tublitz ◽  
M J O'Donnell
Keyword(s):  
Cyclic Gmp ◽  
Physiological Role ◽  
Malpighian Tubule ◽  
Fluid Secretion ◽  
Blood Feeding ◽  
Rhodnius Prolixus ◽  
Malpighian Tubules ◽  
Tubule Fluid ◽  
Secretion Rates

Rhodnius prolixus eliminates NaCl-rich urine at high rates following its infrequent but massive blood meals. This diuresis involves stimulation of Malpighian tubule fluid secretion by diuretic hormones released in response to distention of the abdomen during feeding. The precipitous decline in urine flow that occurs several hours after feeding has been thought until now to result from a decline in diuretic hormone release. We suggest here that insect cardioacceleratory peptide 2b (CAP2b) and cyclic GMP are part of a novel mechanism of anti-diuresis. Secretion rates of 5-hydroxytryptamine-stimulated Malpighian tubules are reduced by low doses of CAP2b or cyclic GMP. Maximal secretion rates are restored by exposing tubules to 1 mmol l-1 cyclic AMP. Levels of cyclic GMP in isolated tubules increase in response to CAP2b, consistent with a role for cyclic GMP as an intracellular second messenger. Levels of cyclic GMP in tubules also increase as urine output rates decline in vivo, suggesting a physiological role for this nucleotide in the termination of diuresis.

scholarly journals Polarization sensitive optical coherence tomography with single input for imaging depth-resolved collagen organizations

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Peijun Tang ◽  
Mitchell A. Kirby ◽  
Nhan Le ◽  
Yuandong Li ◽  
Nicole Zeinstra ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Structural Integrity ◽  
Ex Vivo ◽  
Polarization State ◽  
Transmission Model ◽  
Optical Coherence ◽  
Healthy Human ◽  
Collagen Organization ◽  
Single Input

AbstractCollagen organization plays an important role in maintaining structural integrity and determining tissue function. Polarization-sensitive optical coherence tomography (PSOCT) is a promising noninvasive three-dimensional imaging tool for mapping collagen organization in vivo. While PSOCT systems with multiple polarization inputs have demonstrated the ability to visualize depth-resolved collagen organization, systems, which use a single input polarization state have not yet demonstrated sufficient reconstruction quality. Herein we describe a PSOCT based polarization state transmission model that reveals the depth-dependent polarization state evolution of light backscattered within a birefringent sample. Based on this model, we propose a polarization state tracing method that relies on a discrete differential geometric analysis of the evolution of the polarization state in depth along the Poincare sphere for depth-resolved birefringent imaging using only one single input polarization state. We demonstrate the ability of this method to visualize depth-resolved myocardial architecture in both healthy and infarcted rodent hearts (ex vivo) and collagen structures responsible for skin tension lines at various anatomical locations on the face of a healthy human volunteer (in vivo).

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