6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy
Abstract Background Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease (HFMD), and can cause severe cerebral complications and even fatality in children younger than 5 years old. However, there is no specific medication for EV71 infection in clinical practice...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12866-025-03752-8 |
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| author | Qiao You Jing Wu Ruining Lyu Yurong Cai Na Jiang Ye Liu Fang Zhang Yating He Deyan Chen Zhiwei Wu |
| author_facet | Qiao You Jing Wu Ruining Lyu Yurong Cai Na Jiang Ye Liu Fang Zhang Yating He Deyan Chen Zhiwei Wu |
| author_sort | Qiao You |
| collection | DOAJ |
| description | Abstract Background Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease (HFMD), and can cause severe cerebral complications and even fatality in children younger than 5 years old. However, there is no specific medication for EV71 infection in clinical practice. Our previous studies had identified the 6-thioguanine (6-TG), an FDA-approved anticancer drug, as a potential antiviral agent, but its anti-EV71 activity is largely unknown, therefore, we aim to explore the antiviral effect of 6-TG on EV71. Results 6-TG significantly suppressed EV71 mRNA level, VP1 protein expression, and viral progeny production in HT-29 cells. In EV71-infected HT-29 cells, the 50% cytotoxicity concentration of 6-TG (CC50) was > 2000 µM and the 50% inhibitory concentration of 6-TG against EV71 (IC50) was 0.9302 µM. Interestingly, the selectivity index (SI) value of 6-TG against EV71 was > 2150.1, which was higher than the SI value (> 66.7) of ribavirin. Mechanistically, 6-TG treatment reduced the expression of baculoviral IAP repeat containing 3 (BIRC3), and further inhibited EV71 replication by attenuating BIRC3-mediated the complete autophagy. Conclusions 6-TG exerted a significant inhibitory effect on EV71 infection in vitro and prevented EV71-induced the complete autophagy by decreasing BIRC3 expression. Our work provided a basis for the further development of 6-TG as a therapy for EV71-associated HFMD. |
| format | Article |
| id | doaj-art-2f56146888a94be6841517d91c133229 |
| institution | Kabale University |
| issn | 1471-2180 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Microbiology |
| spelling | doaj-art-2f56146888a94be6841517d91c1332292025-02-02T12:11:12ZengBMCBMC Microbiology1471-21802025-01-0125111510.1186/s12866-025-03752-86-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagyQiao You0Jing Wu1Ruining Lyu2Yurong Cai3Na Jiang4Ye Liu5Fang Zhang6Yating He7Deyan Chen8Zhiwei Wu9Center for Public Health Research, Medical School of Nanjing UniversityCenter for Public Health Research, Medical School of Nanjing UniversityCenter for Public Health Research, Medical School of Nanjing UniversityNingxia Institute of Clinical Medicine, Central Laboratory, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical UniversityCenter for Public Health Research, Medical School of Nanjing UniversityChina Department of Ophthalmology, Tianjin First Central HospitalDepartment of Burn and Plastic Surgery, Affiliated Hospital of Zunyi Medical UniversityCenter for Public Health Research, Medical School of Nanjing UniversityCenter for Public Health Research, Medical School of Nanjing UniversityCenter for Public Health Research, Medical School of Nanjing UniversityAbstract Background Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease (HFMD), and can cause severe cerebral complications and even fatality in children younger than 5 years old. However, there is no specific medication for EV71 infection in clinical practice. Our previous studies had identified the 6-thioguanine (6-TG), an FDA-approved anticancer drug, as a potential antiviral agent, but its anti-EV71 activity is largely unknown, therefore, we aim to explore the antiviral effect of 6-TG on EV71. Results 6-TG significantly suppressed EV71 mRNA level, VP1 protein expression, and viral progeny production in HT-29 cells. In EV71-infected HT-29 cells, the 50% cytotoxicity concentration of 6-TG (CC50) was > 2000 µM and the 50% inhibitory concentration of 6-TG against EV71 (IC50) was 0.9302 µM. Interestingly, the selectivity index (SI) value of 6-TG against EV71 was > 2150.1, which was higher than the SI value (> 66.7) of ribavirin. Mechanistically, 6-TG treatment reduced the expression of baculoviral IAP repeat containing 3 (BIRC3), and further inhibited EV71 replication by attenuating BIRC3-mediated the complete autophagy. Conclusions 6-TG exerted a significant inhibitory effect on EV71 infection in vitro and prevented EV71-induced the complete autophagy by decreasing BIRC3 expression. Our work provided a basis for the further development of 6-TG as a therapy for EV71-associated HFMD.https://doi.org/10.1186/s12866-025-03752-86-thioguanine (6-TG)EV71BIRC3Autophagy |
| spellingShingle | Qiao You Jing Wu Ruining Lyu Yurong Cai Na Jiang Ye Liu Fang Zhang Yating He Deyan Chen Zhiwei Wu 6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy BMC Microbiology 6-thioguanine (6-TG) EV71 BIRC3 Autophagy |
| title | 6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy |
| title_full | 6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy |
| title_fullStr | 6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy |
| title_full_unstemmed | 6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy |
| title_short | 6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy |
| title_sort | 6 thioguanine inhibits ev71 replication by reducing birc3 mediated autophagy |
| topic | 6-thioguanine (6-TG) EV71 BIRC3 Autophagy |
| url | https://doi.org/10.1186/s12866-025-03752-8 |
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