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Infecting mosquitoes alters DENV-2 characteristics and enhances hemorrhage-induction potential in Stat1-/- mice
- Source :
- PLoS Neglected Tropical Diseases, PLoS Neglected Tropical Diseases, Vol 15, Iss 8, p e0009728 (2021)
- Publication Year :
- 2021
- Publisher :
- Public Library of Science, 2021.
-
Abstract
- Dengue is one of the most prevalent arthropod-borne viral diseases in humans. There is still no effective vaccine or treatment to date. Previous studies showed that mosquito-derived factors present in saliva or salivary gland extract (SGE) contribute to the pathogenesis of dengue. In this study, we aimed to investigate the interplay between mosquito vector and DENV and to address the question of whether the mosquito vector alters the virus that leads to consequential disease manifestations in the mammalian host. DENV2 cultured in C6/36 cell line (culture-DENV2) was injected to Aedes aegypti intrathoracically. Saliva was collected from infected mosquitoes 7 days later. Exploiting the sensitivity of Stat1-/- mice to low dose of DENV2 delivered intradermally, we showed that DENV2 collected in infected mosquito saliva (msq-DENV2) induced more severe hemorrhage in mice than their culture counterpart. Msq-DENV2 was characterized by smaller particle size, larger plaque size and more rapid growth in mosquito as well as mammalian cell lines compared to culture-DENV2. In addition, msq-DENV2 was more efficient than culture-DENV2 in inducing Tnf mRNA production by mouse macrophage. Together, our results point to the possibility that the mosquito vector provides an environment that alters DENV2 by changing its growth characteristics as well as its potential to cause disease.<br />Author summary The transmission cycle of dengue virus involves a complex interaction of the virus with the mosquito vector and the human host. DENV enters the mosquito through an infectious blood meal. The virus first infects and replicates in the mosquito midgut before it is translocated to the hemolymph and ultimately reaches the salivary gland. The virus is then released to the saliva and transmitted to the human host through a mosquito blood meal. Previous studies showed that mosquito saliva, salivary gland proteins or mosquito bite modulates arbovirus infection in the mammalian host. Here, we investigate the interplay between the mosquito vector and DENV and address whether the virus is altered in the mosquito vector that consequentially influences disease manifestations in the mammalian host. By excluding the effect of saliva, we demonstrated that after infecting Aedes aegypti, DENV2 acquired the potential to induce more severe hemorrhage in Stat1-/- mice. Msq-DENV2 exhibited smaller particle size, larger plaque size and more rapid growth rate, and was also more efficient in inducing macrophage Tnf production compared to culture-DENV2. Taken together, our data support the notion that mosquito A. aegypti alters DENV2 by changing its growth characteristics as well as its potential to cause disease.
- Subjects :
- RNA viruses
Male
Saliva
Viral Diseases
Pulmonology
Physiology
RC955-962
Disease Vectors
Pathology and Laboratory Medicine
Virus Replication
Vascular Medicine
Mosquitoes
Dengue fever
Dengue Fever
Pathogenesis
Mice
Medical Conditions
Aedes
Arctic medicine. Tropical medicine
Medicine and Health Sciences
Vector (molecular biology)
Mice, Knockout
Salivary gland
Virulence
Eukaryota
Animal Models
Body Fluids
Insects
medicine.anatomical_structure
Infectious Diseases
STAT1 Transcription Factor
Experimental Organism Systems
Medical Microbiology
Viral Pathogens
Viruses
Female
Public aspects of medicine
RA1-1270
Anatomy
Pathogens
Viral Vectors
Research Article
Neglected Tropical Diseases
Arthropoda
Hemorrhage
Mouse Models
Aedes aegypti
Mosquito Vectors
Biology
Research and Analysis Methods
Microbiology
Virus
Cell Line
Respiratory Disorders
Signs and Symptoms
Model Organisms
Virology
medicine
Animals
Humans
Severe Dengue
Microbial Pathogens
Flaviviruses
Public Health, Environmental and Occupational Health
Organisms
Biology and Life Sciences
Dengue Virus
medicine.disease
biology.organism_classification
Tropical Diseases
Invertebrates
Insect Vectors
Species Interactions
Cell culture
Respiratory Infections
Animal Studies
Clinical Medicine
Zoology
Entomology
Viral Transmission and Infection
Subjects
Details
- Language :
- English
- ISSN :
- 19352735 and 19352727
- Volume :
- 15
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....a418ac2b30b53fd866b5b4fd94517cdd