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Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils.
- Source :
-
Journal of virology [J Virol] 2019 Jun 14; Vol. 93 (13). Date of Electronic Publication: 2019 Jun 14 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Saliva from the mosquito vector of flaviviruses is capable of changing the local immune environment, leading to an increase in flavivirus-susceptible cells at the infected bite site. In addition, an antibody response to specific salivary gland (SG) components changes the pathogenesis of flaviviruses in human populations. To investigate whether antigenic SG proteins are capable of enhancing infection with Zika virus (ZIKV), a reemerging flavivirus primarily transmitted by the Aedes aegypti mosquito, we screened for antigenic SG proteins using a yeast display library and demonstrate that a previously undescribed SG protein we term neutrophil stimulating factor 1 (NeSt1) activates primary mouse neutrophils ex vivo Passive immunization against NeSt1 decreases pro-interleukin-1β and CXCL2 expression, prevents macrophages from infiltrating the bite site, protects susceptible IFNAR <superscript>-/-</superscript> IFNGR <superscript>-/-</superscript> (AG129) mice from early ZIKV replication, and ameliorates virus-induced pathogenesis. These findings indicate that NeSt1 stimulates neutrophils at the mosquito bite site to change the immune microenvironment, allowing a higher level of early viral replication and enhancing ZIKV pathogenesis. IMPORTANCE When a Zika virus-infected mosquito bites a person, mosquito saliva is injected into the skin along with the virus. Molecules in this saliva can make virus infection more severe by changing the immune system to make the skin a better place for the virus to replicate. We identified a molecule that activates immune cells, called neutrophils, to recruit other immune cells, called macrophages, that the virus can infect. We named this molecule neutrophil-stimulating factor 1 (NeSt1). When we used antibodies to block NeSt1 in mice and then allowed Zika virus-infected mosquitoes to feed on these mice, they survived much better than mice that do not have antibodies against NeSt1. These findings give us more information about how mosquito saliva enhances virus infection, and it is possible that a vaccine against NeSt1 might protect people against severe Zika virus infection.<br /> (Copyright © 2019 American Society for Microbiology.)
- Subjects :
- Aedes immunology
Animals
Arboviruses
Chemokine CCL2
Chemokine CXCL2 metabolism
Disease Models, Animal
Female
Immunity
Interleukin-1 metabolism
Male
Mice
Mice, Inbred C57BL
Mosquito Vectors virology
Protein Precursors metabolism
RAW 264.7 Cells
Saliva virology
Salivary Glands virology
Virus Replication
Zika Virus pathogenicity
Zika Virus Infection virology
Aedes virology
Neutrophils metabolism
Neutrophils virology
Zika Virus immunology
Zika Virus Infection immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 93
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 30971475
- Full Text :
- https://doi.org/10.1128/JVI.00395-19