Impact of pyriproxyfen on virus behavior: implications for pesticide-induced virulence and mechanism of transmission
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 strat...
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doaj-1ae77d039aae45c19c2596bcd38f9ca32020-11-25T03:48:31ZengBMCVirology Journal1743-422X2020-07-011711810.1186/s12985-020-01378-yImpact of pyriproxyfen on virus behavior: implications for pesticide-induced virulence and mechanism of transmissionPaula A. Faria Waziry0Aarti Raja1Chloe Salmon2Nathalia Aldana3Sruthi Damodar4Andre Rinaldi Fukushima5Bindu S. Mayi6Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern UniversityDepartment of Biological Sciences, Halmos College of Arts and Sciences, Nova Southeastern UniversityPlymouth UniversityDr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern UniversityDr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern UniversityDepartment of Pathology, School of Veterinary Medicine and Animal Science, University of Sao PauloDr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern UniversityAbstract 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.http://link.springer.com/article/10.1186/s12985-020-01378-yNeurovirulencePyriproxyfenPesticidesFlavivirus replicationExtracellular vesiclesWolbachia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Paula A. Faria Waziry Aarti Raja Chloe Salmon Nathalia Aldana Sruthi Damodar Andre Rinaldi Fukushima Bindu S. Mayi |
spellingShingle |
Paula A. Faria Waziry Aarti Raja Chloe Salmon Nathalia Aldana Sruthi Damodar Andre Rinaldi Fukushima Bindu S. Mayi Impact of pyriproxyfen on virus behavior: implications for pesticide-induced virulence and mechanism of transmission Virology Journal Neurovirulence Pyriproxyfen Pesticides Flavivirus replication Extracellular vesicles Wolbachia |
author_facet |
Paula A. Faria Waziry Aarti Raja Chloe Salmon Nathalia Aldana Sruthi Damodar Andre Rinaldi Fukushima Bindu S. Mayi |
author_sort |
Paula A. Faria Waziry |
title |
Impact of pyriproxyfen on virus behavior: implications for pesticide-induced virulence and mechanism of transmission |
title_short |
Impact of pyriproxyfen on virus behavior: implications for pesticide-induced virulence and mechanism of transmission |
title_full |
Impact of pyriproxyfen on virus behavior: implications for pesticide-induced virulence and mechanism of transmission |
title_fullStr |
Impact of pyriproxyfen on virus behavior: implications for pesticide-induced virulence and mechanism of transmission |
title_full_unstemmed |
Impact of pyriproxyfen on virus behavior: implications for pesticide-induced virulence and mechanism of transmission |
title_sort |
impact of pyriproxyfen on virus behavior: implications for pesticide-induced virulence and mechanism of transmission |
publisher |
BMC |
series |
Virology Journal |
issn |
1743-422X |
publishDate |
2020-07-01 |
description |
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. |
topic |
Neurovirulence Pyriproxyfen Pesticides Flavivirus replication Extracellular vesicles Wolbachia |
url |
http://link.springer.com/article/10.1186/s12985-020-01378-y |
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