Biology Faculty Articles
Document Type
Article
Publication Date
7-6-2020
Publication Title
Virology Journal
Keywords
Neurovirulence, Pyriproxyfen, Pesticides, Flavivirus replication, Extracellular vesicles, Wolbachia, Mosquito control
ISSN
1743-422X
Volume
17
Issue/No.
1
First Page
93
Abstract
Background
More than 3 years since the last Zika virus (ZIKV) outbreak in Brazil, researchers are still deciphering the molecular mechanisms of neurovirulence and vertical transmission, as well as the best way to control spread of ZIKV, a flavivirus. The use of pesticides was the main strategy of mosquito control during the last ZIKV outbreak.
Methods
We used vesicular stomatitis virus (VSV) tagged with green fluorescent protein (GFP) as our prototypical virus to study the impact of insecticide pyriproxyfen (PPF). VZV-GFP infected and uninfected Jurkat, HeLa and trophoblast cells were treated with PPF and compared to untreated cells (control). Cell viability was determined by the MTT assay. Cell morphology, presence of extracellular vesicles (EVs), virus infection/GFP expression as well as active mitochondrial levels/localization were examined by confocal microscopy.
Results
PPF, which was used to control mosquito populations in Brazil prior to the ZIKV outbreak, enhances VSV replication and has cell membrane-altering properties in the presence of virus. PPF causes enhanced viral replication and formation of large EVs, loaded with virus as well as mitochondria. Treatment of trophoblasts or HeLa cells with increasing concentrations of PPF does not alter cell viability, however, it proportionately increases Jurkat cell viability. Increasing concentrations of PPF followed by VSV infection does not interfere with HeLa cell viability. Both Jurkats and trophoblasts show proportionately increased cell death with increased concentrations of PPF in the presence of virus.
Conclusions
We hypothesize that PPF disrupts the lipid microenvironment of mammalian cells, thereby interfering with pathways of viral replication. PPF lowers viability of trophoblasts and Jurkats in the presence of VSV, implying that the combination renders immune system impairment in infected individuals as well as enhanced vulnerability of fetuses towards viral vertical transmission. We hypothesize that similar viruses such as ZIKV may be vertically transmitted via EV-to-cell contact when exposed to PPF, thereby bypassing immune detection. The impact of pesticides on viral replication must be fully investigated before large scale use in future outbreaks of mosquito borne viruses.
Additional Comments
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
NSUWorks Citation
Waziry, Paula A. Faria; Aarti Raja; Chloe Salmon; Nathalia Aldana; Sruthi Damodar; Andre Rinaldi Fukushima; and Bindu S. Mayi. 2020. "Impact of pyriproxyfen on virus behavior: implications for pesticide-induced virulence and mechanism of transmission." Virology Journal 17, (1): 93. doi:10.1186/s12985-020-01378-y.
DOI
10.1186/s12985-020-01378-y
Comments
We thank Hoang Nguyen, Devina Basdeo and Mareena Kashif-Shafiq (Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Clearwater) for their review of the manuscript.