PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target
Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than 5 y old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-12-01
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| Series: | Virulence |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21505594.2017.1326443 |
| _version_ | 1818609128399962112 |
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| author | Yuebang Yin Wen Dang Xinying Zhou Lei Xu Wenshi Wang Wanlu Cao Sunrui Chen Junhong Su Xuepeng Cai Shaobo Xiao Maikel P. Peppelenbosch Qiuwei Pan |
| author_facet | Yuebang Yin Wen Dang Xinying Zhou Lei Xu Wenshi Wang Wanlu Cao Sunrui Chen Junhong Su Xuepeng Cai Shaobo Xiao Maikel P. Peppelenbosch Qiuwei Pan |
| author_sort | Yuebang Yin |
| collection | DOAJ |
| description | Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than 5 y old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies. PI3K-Akt-mTOR signaling pathway plays a vital role in regulating the infection course of many viruses. In this study, we have dissected the effects of PI3K-Akt-mTOR signaling pathway on rotavirus infection using both conventional cell culture models and a 3D model of human primary intestinal organoids. We found that PI3K-Akt-mTOR signaling is essential in sustaining rotavirus infection. Thus, blocking the key elements of this pathway, including PI3K, mTOR and 4E-BP1, has resulted in potent anti-rotavirus activity. Importantly, a clinically used mTOR inhibitor, rapamycin, potently inhibited both experimental and patient-derived rotavirus strains. This effect involves 4E-BP1 mediated induction of autophagy, which in turn exerts anti-rotavirus effects. These results revealed new insights on rotavirus-host interactions and provided new avenues for antiviral drug development. |
| first_indexed | 2024-12-16T14:53:37Z |
| format | Article |
| id | doaj.art-1980859b94b84e4ea184654b34f6c182 |
| institution | Directory Open Access Journal |
| issn | 2150-5594 2150-5608 |
| language | English |
| last_indexed | 2024-12-16T14:53:37Z |
| publishDate | 2018-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj.art-1980859b94b84e4ea184654b34f6c1822022-12-21T22:27:30ZengTaylor & Francis GroupVirulence2150-55942150-56082018-12-0191839810.1080/21505594.2017.13264431326443PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral targetYuebang Yin0Wen Dang1Xinying Zhou2Lei Xu3Wenshi Wang4Wanlu Cao5Sunrui Chen6Junhong Su7Xuepeng Cai8Shaobo Xiao9Maikel P. Peppelenbosch10Qiuwei Pan11Erasmus MC-University Medical CenterErasmus MC-University Medical CenterErasmus MC-University Medical CenterErasmus MC-University Medical CenterErasmus MC-University Medical CenterErasmus MC-University Medical CenterErasmus MC-University Medical CenterMedical Faculty, Kunming University of Science and TechnologyState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS)State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityErasmus MC-University Medical CenterErasmus MC-University Medical CenterRotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than 5 y old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies. PI3K-Akt-mTOR signaling pathway plays a vital role in regulating the infection course of many viruses. In this study, we have dissected the effects of PI3K-Akt-mTOR signaling pathway on rotavirus infection using both conventional cell culture models and a 3D model of human primary intestinal organoids. We found that PI3K-Akt-mTOR signaling is essential in sustaining rotavirus infection. Thus, blocking the key elements of this pathway, including PI3K, mTOR and 4E-BP1, has resulted in potent anti-rotavirus activity. Importantly, a clinically used mTOR inhibitor, rapamycin, potently inhibited both experimental and patient-derived rotavirus strains. This effect involves 4E-BP1 mediated induction of autophagy, which in turn exerts anti-rotavirus effects. These results revealed new insights on rotavirus-host interactions and provided new avenues for antiviral drug development.http://dx.doi.org/10.1080/21505594.2017.1326443autophagyintestinal organoidsPI3K-Akt-mTOR-4E-BP1 pathwayrotavirus |
| spellingShingle | Yuebang Yin Wen Dang Xinying Zhou Lei Xu Wenshi Wang Wanlu Cao Sunrui Chen Junhong Su Xuepeng Cai Shaobo Xiao Maikel P. Peppelenbosch Qiuwei Pan PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target Virulence autophagy intestinal organoids PI3K-Akt-mTOR-4E-BP1 pathway rotavirus |
| title | PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target |
| title_full | PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target |
| title_fullStr | PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target |
| title_full_unstemmed | PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target |
| title_short | PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target |
| title_sort | pi3k akt mtor axis sustains rotavirus infection via the 4e bp1 mediated autophagy pathway and represents an antiviral target |
| topic | autophagy intestinal organoids PI3K-Akt-mTOR-4E-BP1 pathway rotavirus |
| url | http://dx.doi.org/10.1080/21505594.2017.1326443 |
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