Peste des Petits Ruminants Virus Enters Caprine Endometrial Epithelial Cells via the Caveolae-Mediated Endocytosis Pathway
Peste des petits ruminants virus (PPRV) causes an acute and highly contagious disease of sheep and goats and has spread with alarming speed around the world. The pathology of Peste des petits ruminants is linked to retrogressive changes and necrotic lesions in lymphoid tissues and epithelial cells....
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-02-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00210/full |
| _version_ | 1819092385432338432 |
|---|---|
| author | Bo Yang Bo Yang Xuefeng Qi Hui Guo Peilong Jia Shuying Chen Zhijie Chen Zhijie Chen Ting Wang Jingyu Wang Qinghong Xue |
| author_facet | Bo Yang Bo Yang Xuefeng Qi Hui Guo Peilong Jia Shuying Chen Zhijie Chen Zhijie Chen Ting Wang Jingyu Wang Qinghong Xue |
| author_sort | Bo Yang |
| collection | DOAJ |
| description | Peste des petits ruminants virus (PPRV) causes an acute and highly contagious disease of sheep and goats and has spread with alarming speed around the world. The pathology of Peste des petits ruminants is linked to retrogressive changes and necrotic lesions in lymphoid tissues and epithelial cells. However, the process of PPRV entry into host epithelial cells remains largely unknown. Here, we performed a comprehensive study of the entry mechanism of PPRV into caprine endometrial epithelial cells (EECs). We clearly demonstrated that PPRV internalization was inhibited by chloroquine and ammonium chloride, which elevate the pH of various organelles. However, PPRV entry was not affected by chlorpromazine and knockdown of the clathrin heavy chain in EECs. In addition, we found that the internalization of PPRV was dependent on dynamin and membrane cholesterol and was suppressed by silencing of caveolin-1. Macropinocytosis did not play a role, but phosphatidylinositol 3-kinase (PI3K) was required for PPRV internalization. Cell type and receptor-dependent differences indicated that PPRV entry into caprine fetal fibroblast cells (FFCs) occurred via a different route. Taken together, our findings demonstrate that PPRV enters EECs through a cholesterol-dependent caveolae-mediated uptake mechanism that is pH-dependent and requires dynamin and PI3K but is independent of clathrin. This potentially provides insight into the entry mechanisms of other morbilliviruses. |
| first_indexed | 2024-12-21T22:54:47Z |
| format | Article |
| id | doaj.art-75487b427f1446b3bd81abedbf119a12 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-21T22:54:47Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-75487b427f1446b3bd81abedbf119a122022-12-21T18:47:29ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-02-01910.3389/fmicb.2018.00210328421Peste des Petits Ruminants Virus Enters Caprine Endometrial Epithelial Cells via the Caveolae-Mediated Endocytosis PathwayBo Yang0Bo Yang1Xuefeng Qi2Hui Guo3Peilong Jia4Shuying Chen5Zhijie Chen6Zhijie Chen7Ting Wang8Jingyu Wang9Qinghong Xue10China Institute of Veterinary Drug Control, Beijing, ChinaCollege of Veterinary Medicine, Northwest A&F University, Xianyang, ChinaCollege of Veterinary Medicine, Northwest A&F University, Xianyang, ChinaChina Institute of Veterinary Drug Control, Beijing, ChinaCollege of Veterinary Medicine, Northwest A&F University, Xianyang, ChinaCollege of Veterinary Medicine, Northwest A&F University, Xianyang, ChinaChina Institute of Veterinary Drug Control, Beijing, ChinaCollege of Veterinary Medicine, Northwest A&F University, Xianyang, ChinaCollege of Veterinary Medicine, Northwest A&F University, Xianyang, ChinaCollege of Veterinary Medicine, Northwest A&F University, Xianyang, ChinaChina Institute of Veterinary Drug Control, Beijing, ChinaPeste des petits ruminants virus (PPRV) causes an acute and highly contagious disease of sheep and goats and has spread with alarming speed around the world. The pathology of Peste des petits ruminants is linked to retrogressive changes and necrotic lesions in lymphoid tissues and epithelial cells. However, the process of PPRV entry into host epithelial cells remains largely unknown. Here, we performed a comprehensive study of the entry mechanism of PPRV into caprine endometrial epithelial cells (EECs). We clearly demonstrated that PPRV internalization was inhibited by chloroquine and ammonium chloride, which elevate the pH of various organelles. However, PPRV entry was not affected by chlorpromazine and knockdown of the clathrin heavy chain in EECs. In addition, we found that the internalization of PPRV was dependent on dynamin and membrane cholesterol and was suppressed by silencing of caveolin-1. Macropinocytosis did not play a role, but phosphatidylinositol 3-kinase (PI3K) was required for PPRV internalization. Cell type and receptor-dependent differences indicated that PPRV entry into caprine fetal fibroblast cells (FFCs) occurred via a different route. Taken together, our findings demonstrate that PPRV enters EECs through a cholesterol-dependent caveolae-mediated uptake mechanism that is pH-dependent and requires dynamin and PI3K but is independent of clathrin. This potentially provides insight into the entry mechanisms of other morbilliviruses.http://journal.frontiersin.org/article/10.3389/fmicb.2018.00210/fullPPRVentrycaprine endometrial epithelial cellscaveolinendocytosis |
| spellingShingle | Bo Yang Bo Yang Xuefeng Qi Hui Guo Peilong Jia Shuying Chen Zhijie Chen Zhijie Chen Ting Wang Jingyu Wang Qinghong Xue Peste des Petits Ruminants Virus Enters Caprine Endometrial Epithelial Cells via the Caveolae-Mediated Endocytosis Pathway Frontiers in Microbiology PPRV entry caprine endometrial epithelial cells caveolin endocytosis |
| title | Peste des Petits Ruminants Virus Enters Caprine Endometrial Epithelial Cells via the Caveolae-Mediated Endocytosis Pathway |
| title_full | Peste des Petits Ruminants Virus Enters Caprine Endometrial Epithelial Cells via the Caveolae-Mediated Endocytosis Pathway |
| title_fullStr | Peste des Petits Ruminants Virus Enters Caprine Endometrial Epithelial Cells via the Caveolae-Mediated Endocytosis Pathway |
| title_full_unstemmed | Peste des Petits Ruminants Virus Enters Caprine Endometrial Epithelial Cells via the Caveolae-Mediated Endocytosis Pathway |
| title_short | Peste des Petits Ruminants Virus Enters Caprine Endometrial Epithelial Cells via the Caveolae-Mediated Endocytosis Pathway |
| title_sort | peste des petits ruminants virus enters caprine endometrial epithelial cells via the caveolae mediated endocytosis pathway |
| topic | PPRV entry caprine endometrial epithelial cells caveolin endocytosis |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00210/full |
| work_keys_str_mv | AT boyang pestedespetitsruminantsvirusenterscaprineendometrialepithelialcellsviathecaveolaemediatedendocytosispathway AT boyang pestedespetitsruminantsvirusenterscaprineendometrialepithelialcellsviathecaveolaemediatedendocytosispathway AT xuefengqi pestedespetitsruminantsvirusenterscaprineendometrialepithelialcellsviathecaveolaemediatedendocytosispathway AT huiguo pestedespetitsruminantsvirusenterscaprineendometrialepithelialcellsviathecaveolaemediatedendocytosispathway AT peilongjia pestedespetitsruminantsvirusenterscaprineendometrialepithelialcellsviathecaveolaemediatedendocytosispathway AT shuyingchen pestedespetitsruminantsvirusenterscaprineendometrialepithelialcellsviathecaveolaemediatedendocytosispathway AT zhijiechen pestedespetitsruminantsvirusenterscaprineendometrialepithelialcellsviathecaveolaemediatedendocytosispathway AT zhijiechen pestedespetitsruminantsvirusenterscaprineendometrialepithelialcellsviathecaveolaemediatedendocytosispathway AT tingwang pestedespetitsruminantsvirusenterscaprineendometrialepithelialcellsviathecaveolaemediatedendocytosispathway AT jingyuwang pestedespetitsruminantsvirusenterscaprineendometrialepithelialcellsviathecaveolaemediatedendocytosispathway AT qinghongxue pestedespetitsruminantsvirusenterscaprineendometrialepithelialcellsviathecaveolaemediatedendocytosispathway |