Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting Inflammation
Lung tumor-promoting environmental exposures and γherpesvirus infections are associated with Type 17 inflammation. To test the effect of γherpesvirus infection in promoting lung tumorigenesis, we infected mutant K-Ras-expressing (K-Ras<sup>LA1</sup>) mice with the murine γherpesvirus MHV...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-08-01
|
| Series: | Pathogens |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-0817/13/9/747 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850259999047024640 |
|---|---|
| author | Sudurika S. Mukhopadhyay Kenneth F. Swan Gabriella Pridjian Jay K. Kolls Yan Zhuang Qinyan Yin Joseph A. Lasky Erik Flemington Cindy A. Morris Zhen Lin Gilbert F. Morris |
| author_facet | Sudurika S. Mukhopadhyay Kenneth F. Swan Gabriella Pridjian Jay K. Kolls Yan Zhuang Qinyan Yin Joseph A. Lasky Erik Flemington Cindy A. Morris Zhen Lin Gilbert F. Morris |
| author_sort | Sudurika S. Mukhopadhyay |
| collection | DOAJ |
| description | Lung tumor-promoting environmental exposures and γherpesvirus infections are associated with Type 17 inflammation. To test the effect of γherpesvirus infection in promoting lung tumorigenesis, we infected mutant K-Ras-expressing (K-Ras<sup>LA1</sup>) mice with the murine γherpesvirus MHV68 via oropharyngeal aspiration. After 7 weeks, the infected mice displayed a more than 2-fold increase in lung tumors relative to their K-Ras<sup>LA1</sup> uninfected littermates. Assessment of cytokines in the lung revealed that expression of Type 17 cytokines (<i>Il-6</i>, <i>Cxcl1</i>, <i>Csf3</i>) peaked at day 7 post-infection. These observations correlated with the post-infection appearance of known immune mediators of tumor promotion via IL-17A in the lungs of tumor-bearing mice. Surprisingly, <i>Cd84</i>, an immune cell marker mRNA, did not increase in MHV68-infected wild-type mice lacking lung tumors. Csf3 and Cxcl1 protein levels increased more in the lungs of infected K-Ras<sup>LA1</sup> mice relative to infected wild-type littermates. Flow cytometric and transcriptomic analyses indicated that the infected K-Ras<sup>LA1</sup> mice had increased Ly6G<sup>dim</sup>/Ly6C<sup>hi</sup> immune cells in the lung relative to levels seen in uninfected control K-Ras<sup>LA1</sup> mice. Selective methylation of adenosines (m<sup>6</sup>A modification) in immune-cell-enriched mRNAs appeared to correlate with inflammatory infiltrates in the lung. These observations implicate γherpesvirus infection in lung tumor promotion and selective accumulation of immune cells in the lung that appears to be associated with m<sup>6</sup>A modification of mRNAs in those cells. |
| format | Article |
| id | doaj-art-264b9a65cb2f4652827b5dcff367dffb |
| institution | OA Journals |
| issn | 2076-0817 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj-art-264b9a65cb2f4652827b5dcff367dffb2025-08-20T01:55:45ZengMDPI AGPathogens2076-08172024-08-0113974710.3390/pathogens13090747Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting InflammationSudurika S. Mukhopadhyay0Kenneth F. Swan1Gabriella Pridjian2Jay K. Kolls3Yan Zhuang4Qinyan Yin5Joseph A. Lasky6Erik Flemington7Cindy A. Morris8Zhen Lin9Gilbert F. Morris10Departments of Microbiology & Immunology and Pathology & Laboratory Medicine, School of Medicine, Tulane University, New Orleans, LA 70118, USADepartment of Obstetrics & Gynecology, School of Medicine, Tulane University, New Orleans, LA 70118, USADepartment of Obstetrics & Gynecology, School of Medicine, Tulane University, New Orleans, LA 70118, USADepartments of Medicine & Pediatrics, School of Medicine, Tulane University, New Orleans, LA 70118, USADivision of Pulmonary, Critical Care and Environmental Medicine, Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70118, USADivision of Pulmonary, Critical Care and Environmental Medicine, Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70118, USADivision of Pulmonary, Critical Care and Environmental Medicine, Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70118, USADepartment of Pathology & Laboratory Medicine, School of Medicine, Tulane Cancer Center, Tulane University, New Orleans, LA 70118, USADepartment of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70118, USADepartment of Pathology & Laboratory Medicine, School of Medicine, Tulane Cancer Center, Tulane University, New Orleans, LA 70118, USADepartment of Pathology & Laboratory Medicine, School of Medicine, Tulane Cancer Center, Tulane University, New Orleans, LA 70118, USALung tumor-promoting environmental exposures and γherpesvirus infections are associated with Type 17 inflammation. To test the effect of γherpesvirus infection in promoting lung tumorigenesis, we infected mutant K-Ras-expressing (K-Ras<sup>LA1</sup>) mice with the murine γherpesvirus MHV68 via oropharyngeal aspiration. After 7 weeks, the infected mice displayed a more than 2-fold increase in lung tumors relative to their K-Ras<sup>LA1</sup> uninfected littermates. Assessment of cytokines in the lung revealed that expression of Type 17 cytokines (<i>Il-6</i>, <i>Cxcl1</i>, <i>Csf3</i>) peaked at day 7 post-infection. These observations correlated with the post-infection appearance of known immune mediators of tumor promotion via IL-17A in the lungs of tumor-bearing mice. Surprisingly, <i>Cd84</i>, an immune cell marker mRNA, did not increase in MHV68-infected wild-type mice lacking lung tumors. Csf3 and Cxcl1 protein levels increased more in the lungs of infected K-Ras<sup>LA1</sup> mice relative to infected wild-type littermates. Flow cytometric and transcriptomic analyses indicated that the infected K-Ras<sup>LA1</sup> mice had increased Ly6G<sup>dim</sup>/Ly6C<sup>hi</sup> immune cells in the lung relative to levels seen in uninfected control K-Ras<sup>LA1</sup> mice. Selective methylation of adenosines (m<sup>6</sup>A modification) in immune-cell-enriched mRNAs appeared to correlate with inflammatory infiltrates in the lung. These observations implicate γherpesvirus infection in lung tumor promotion and selective accumulation of immune cells in the lung that appears to be associated with m<sup>6</sup>A modification of mRNAs in those cells.https://www.mdpi.com/2076-0817/13/9/747γherpesvirusEBVMHV68MDSCstumorigenesisType 17 inflammation |
| spellingShingle | Sudurika S. Mukhopadhyay Kenneth F. Swan Gabriella Pridjian Jay K. Kolls Yan Zhuang Qinyan Yin Joseph A. Lasky Erik Flemington Cindy A. Morris Zhen Lin Gilbert F. Morris Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting Inflammation Pathogens γherpesvirus EBV MHV68 MDSCs tumorigenesis Type 17 inflammation |
| title | Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting Inflammation |
| title_full | Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting Inflammation |
| title_fullStr | Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting Inflammation |
| title_full_unstemmed | Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting Inflammation |
| title_short | Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting Inflammation |
| title_sort | gammaherpesvirus infection stimulates lung tumor promoting inflammation |
| topic | γherpesvirus EBV MHV68 MDSCs tumorigenesis Type 17 inflammation |
| url | https://www.mdpi.com/2076-0817/13/9/747 |
| work_keys_str_mv | AT sudurikasmukhopadhyay gammaherpesvirusinfectionstimulateslungtumorpromotinginflammation AT kennethfswan gammaherpesvirusinfectionstimulateslungtumorpromotinginflammation AT gabriellapridjian gammaherpesvirusinfectionstimulateslungtumorpromotinginflammation AT jaykkolls gammaherpesvirusinfectionstimulateslungtumorpromotinginflammation AT yanzhuang gammaherpesvirusinfectionstimulateslungtumorpromotinginflammation AT qinyanyin gammaherpesvirusinfectionstimulateslungtumorpromotinginflammation AT josephalasky gammaherpesvirusinfectionstimulateslungtumorpromotinginflammation AT erikflemington gammaherpesvirusinfectionstimulateslungtumorpromotinginflammation AT cindyamorris gammaherpesvirusinfectionstimulateslungtumorpromotinginflammation AT zhenlin gammaherpesvirusinfectionstimulateslungtumorpromotinginflammation AT gilbertfmorris gammaherpesvirusinfectionstimulateslungtumorpromotinginflammation |