Common Chemical Plasticizer Di(2-Ethhylhexyl) Phthalate Exposure Exacerbates Coxsackievirus B3 Infection
Di(2-ethhylhexyl) phthalate (DEHP) is a common plastic rubberizer. DEHP leaches from plastic matrices and is under increasing scrutiny as numerous studies have linked it to negative human health manifestations. Coxsackievirus B3 (CVB) is a human pathogen that typically causes subclinical infections...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/16/12/1821 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850035941319639040 |
|---|---|
| author | Ramina Kordbacheh Madelyn Ashley William D. Cutts Taryn E. Keyzer Shruti Chatterjee Tyler J. Altman Natalie G. Alexander Timothy E. Sparer Brandon J. Kim Jon Sin |
| author_facet | Ramina Kordbacheh Madelyn Ashley William D. Cutts Taryn E. Keyzer Shruti Chatterjee Tyler J. Altman Natalie G. Alexander Timothy E. Sparer Brandon J. Kim Jon Sin |
| author_sort | Ramina Kordbacheh |
| collection | DOAJ |
| description | Di(2-ethhylhexyl) phthalate (DEHP) is a common plastic rubberizer. DEHP leaches from plastic matrices and is under increasing scrutiny as numerous studies have linked it to negative human health manifestations. Coxsackievirus B3 (CVB) is a human pathogen that typically causes subclinical infections but can sometimes cause severe diseases such as pancreatitis, myocarditis, and meningoencephalitis. Though CVB infections are common, severe illness is relatively rare, and it is unclear what factors mediate disease severity. In this study, we sought to determine the effects that DEHP has on CVB infection in a variety of human cell types to evaluate whether this plastic-derived pollutant could represent a proviral environmental factor. Methods: HeLa cervical cancer cells, human induced pluripotent stem cell-derived brain-like endothelial cells (iBECs), and Caco-2 colon carcinoma cells were exposed to 40 µg/mL DEHP for 24 h prior to infecting with enhanced green fluorescent protein (EGFP)-expressing CVB. The severity of the infection was evaluated via fluorescence microscopy and flow cytometry-based viral EGFP detection, viral plaque assay on tissue culture media, and Western blotting to detect VP1 viral capsid protein. Interferon-associated proteins such as interferon regulatory factor (IRF) 3, IRF7, interferon-induced transmembrane (IFITM) 2, and IFITM3 were measured by Western blotting. The roles of IFITM2 and IFITM3 in the context of CVB infection were evaluated via siRNA silencing. Results: We found that DEHP drastically increased CVB infection in each of the cell types we tested, and, while the cellular processes underlying DEHP’s proviral properties were not entirely clear, we observed that DEHP may subvert CVB-induced interferon signaling and elevate levels of IFITMs, which appeared to bolster CVB infection. Conclusions: DEHP may represent a major environmental factor associated with the severity of CVB infection. Further understanding of how DEHP exacerbates infection may better elucidate its potential role as a proviral environmental factor. |
| format | Article |
| id | doaj-art-8ba11abfdcfb49f6b20b4b1f03ef37d0 |
| institution | DOAJ |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-8ba11abfdcfb49f6b20b4b1f03ef37d02025-08-20T02:57:21ZengMDPI AGViruses1999-49152024-11-011612182110.3390/v16121821Common Chemical Plasticizer Di(2-Ethhylhexyl) Phthalate Exposure Exacerbates Coxsackievirus B3 InfectionRamina Kordbacheh0Madelyn Ashley1William D. Cutts2Taryn E. Keyzer3Shruti Chatterjee4Tyler J. Altman5Natalie G. Alexander6Timothy E. Sparer7Brandon J. Kim8Jon Sin9Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USADepartment of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USADepartment of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USADepartment of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USADepartment of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USADepartment of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USADepartment of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USADepartment of Microbiology, University of Tennessee, Knoxville, TN 37996, USADepartment of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USADepartment of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USADi(2-ethhylhexyl) phthalate (DEHP) is a common plastic rubberizer. DEHP leaches from plastic matrices and is under increasing scrutiny as numerous studies have linked it to negative human health manifestations. Coxsackievirus B3 (CVB) is a human pathogen that typically causes subclinical infections but can sometimes cause severe diseases such as pancreatitis, myocarditis, and meningoencephalitis. Though CVB infections are common, severe illness is relatively rare, and it is unclear what factors mediate disease severity. In this study, we sought to determine the effects that DEHP has on CVB infection in a variety of human cell types to evaluate whether this plastic-derived pollutant could represent a proviral environmental factor. Methods: HeLa cervical cancer cells, human induced pluripotent stem cell-derived brain-like endothelial cells (iBECs), and Caco-2 colon carcinoma cells were exposed to 40 µg/mL DEHP for 24 h prior to infecting with enhanced green fluorescent protein (EGFP)-expressing CVB. The severity of the infection was evaluated via fluorescence microscopy and flow cytometry-based viral EGFP detection, viral plaque assay on tissue culture media, and Western blotting to detect VP1 viral capsid protein. Interferon-associated proteins such as interferon regulatory factor (IRF) 3, IRF7, interferon-induced transmembrane (IFITM) 2, and IFITM3 were measured by Western blotting. The roles of IFITM2 and IFITM3 in the context of CVB infection were evaluated via siRNA silencing. Results: We found that DEHP drastically increased CVB infection in each of the cell types we tested, and, while the cellular processes underlying DEHP’s proviral properties were not entirely clear, we observed that DEHP may subvert CVB-induced interferon signaling and elevate levels of IFITMs, which appeared to bolster CVB infection. Conclusions: DEHP may represent a major environmental factor associated with the severity of CVB infection. Further understanding of how DEHP exacerbates infection may better elucidate its potential role as a proviral environmental factor.https://www.mdpi.com/1999-4915/16/12/1821coxsackievirus B3 (CVB)Di(2-ethhylhexyl) phthalate (DEHP)proviralenvironmental factors |
| spellingShingle | Ramina Kordbacheh Madelyn Ashley William D. Cutts Taryn E. Keyzer Shruti Chatterjee Tyler J. Altman Natalie G. Alexander Timothy E. Sparer Brandon J. Kim Jon Sin Common Chemical Plasticizer Di(2-Ethhylhexyl) Phthalate Exposure Exacerbates Coxsackievirus B3 Infection Viruses coxsackievirus B3 (CVB) Di(2-ethhylhexyl) phthalate (DEHP) proviral environmental factors |
| title | Common Chemical Plasticizer Di(2-Ethhylhexyl) Phthalate Exposure Exacerbates Coxsackievirus B3 Infection |
| title_full | Common Chemical Plasticizer Di(2-Ethhylhexyl) Phthalate Exposure Exacerbates Coxsackievirus B3 Infection |
| title_fullStr | Common Chemical Plasticizer Di(2-Ethhylhexyl) Phthalate Exposure Exacerbates Coxsackievirus B3 Infection |
| title_full_unstemmed | Common Chemical Plasticizer Di(2-Ethhylhexyl) Phthalate Exposure Exacerbates Coxsackievirus B3 Infection |
| title_short | Common Chemical Plasticizer Di(2-Ethhylhexyl) Phthalate Exposure Exacerbates Coxsackievirus B3 Infection |
| title_sort | common chemical plasticizer di 2 ethhylhexyl phthalate exposure exacerbates coxsackievirus b3 infection |
| topic | coxsackievirus B3 (CVB) Di(2-ethhylhexyl) phthalate (DEHP) proviral environmental factors |
| url | https://www.mdpi.com/1999-4915/16/12/1821 |
| work_keys_str_mv | AT raminakordbacheh commonchemicalplasticizerdi2ethhylhexylphthalateexposureexacerbatescoxsackievirusb3infection AT madelynashley commonchemicalplasticizerdi2ethhylhexylphthalateexposureexacerbatescoxsackievirusb3infection AT williamdcutts commonchemicalplasticizerdi2ethhylhexylphthalateexposureexacerbatescoxsackievirusb3infection AT tarynekeyzer commonchemicalplasticizerdi2ethhylhexylphthalateexposureexacerbatescoxsackievirusb3infection AT shrutichatterjee commonchemicalplasticizerdi2ethhylhexylphthalateexposureexacerbatescoxsackievirusb3infection AT tylerjaltman commonchemicalplasticizerdi2ethhylhexylphthalateexposureexacerbatescoxsackievirusb3infection AT nataliegalexander commonchemicalplasticizerdi2ethhylhexylphthalateexposureexacerbatescoxsackievirusb3infection AT timothyesparer commonchemicalplasticizerdi2ethhylhexylphthalateexposureexacerbatescoxsackievirusb3infection AT brandonjkim commonchemicalplasticizerdi2ethhylhexylphthalateexposureexacerbatescoxsackievirusb3infection AT jonsin commonchemicalplasticizerdi2ethhylhexylphthalateexposureexacerbatescoxsackievirusb3infection |