Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in Marmosets
The major mechanism for determination of HCV infection outcomes has not been fully described, particularly in the early phase of the “window-period” of infection. Based on two groups of marmosets infected with HCV-CE1E2p7/GBV-B chimeric virus (HCV chimera) or GBV-B, the immune mechanism correlating...
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MDPI AG
2023-04-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/5/1082 |
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| author | Bochao Liu Enhui Zhang Xiaorui Ma Shengxue Luo Chong Wang Ling Zhang Wenjing Wang Yongshui Fu Jean-Pierre Allain Chengyao Li Tingting Li |
| author_facet | Bochao Liu Enhui Zhang Xiaorui Ma Shengxue Luo Chong Wang Ling Zhang Wenjing Wang Yongshui Fu Jean-Pierre Allain Chengyao Li Tingting Li |
| author_sort | Bochao Liu |
| collection | DOAJ |
| description | The major mechanism for determination of HCV infection outcomes has not been fully described, particularly in the early phase of the “window-period” of infection. Based on two groups of marmosets infected with HCV-CE1E2p7/GBV-B chimeric virus (HCV chimera) or GBV-B, the immune mechanism correlating with the different outcomes of virus infections was explored in this study. HCV chimera containing the entire HCV core and envelope proteins (CE1E2p7) and GBV-B RNA were intrahepatically injected into four marmosets in each group, respectively. Blood samples were taken from individual animals in an interval of 2 weeks. Viral load and specific T cell responses were detected in two groups of HCV chimera- and GBV-B-infected marmosets. HCV chimera-infected marmosets appeared to have a virally persistent infection over 6 months post inoculation of the virus. Of these, the specific IFN-γ-secretion T cell response slowly developed over 13 to 19 weeks and was maintained at a relatively low level with 40–70 SFC/10<sup>6</sup> PBMCs, while the specific Treg cell response was rapidly activated over 3 weeks and was maintained at a high level around 5% among lymphocytes. In contrast, GBV-B-infected marmosets presented spontaneous viral clearance within 6 months; the specific IFN-γ-secretion T cell response was quickly established over 5 to 7 weeks and was maintained at a high level with 50–130 SFC/10<sup>6</sup> PBMCs, while the specific Treg cell response was inactivated and maintained at a baseline below 3% among lymphocytes. In conclusion, the HCV structural proteins inducing immune suppression in the early phase of HCV infection contributed to the viral persistence, of which the activation of Treg cells might play an important role in the inhibition of an effective T cell antiviral response. |
| first_indexed | 2024-03-11T03:14:37Z |
| format | Article |
| id | doaj.art-a79b97749181447a8307cb79622f4dec |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T03:14:37Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a79b97749181447a8307cb79622f4dec2023-11-18T03:38:42ZengMDPI AGViruses1999-49152023-04-01155108210.3390/v15051082Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in MarmosetsBochao Liu0Enhui Zhang1Xiaorui Ma2Shengxue Luo3Chong Wang4Ling Zhang5Wenjing Wang6Yongshui Fu7Jean-Pierre Allain8Chengyao Li9Tingting Li10Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaGuangzhou Blood Center, Guangzhou 510095, ChinaDivision of Transfusion Medicine, University of Cambridge, Cambridge CB2 2PT, UKDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaThe major mechanism for determination of HCV infection outcomes has not been fully described, particularly in the early phase of the “window-period” of infection. Based on two groups of marmosets infected with HCV-CE1E2p7/GBV-B chimeric virus (HCV chimera) or GBV-B, the immune mechanism correlating with the different outcomes of virus infections was explored in this study. HCV chimera containing the entire HCV core and envelope proteins (CE1E2p7) and GBV-B RNA were intrahepatically injected into four marmosets in each group, respectively. Blood samples were taken from individual animals in an interval of 2 weeks. Viral load and specific T cell responses were detected in two groups of HCV chimera- and GBV-B-infected marmosets. HCV chimera-infected marmosets appeared to have a virally persistent infection over 6 months post inoculation of the virus. Of these, the specific IFN-γ-secretion T cell response slowly developed over 13 to 19 weeks and was maintained at a relatively low level with 40–70 SFC/10<sup>6</sup> PBMCs, while the specific Treg cell response was rapidly activated over 3 weeks and was maintained at a high level around 5% among lymphocytes. In contrast, GBV-B-infected marmosets presented spontaneous viral clearance within 6 months; the specific IFN-γ-secretion T cell response was quickly established over 5 to 7 weeks and was maintained at a high level with 50–130 SFC/10<sup>6</sup> PBMCs, while the specific Treg cell response was inactivated and maintained at a baseline below 3% among lymphocytes. In conclusion, the HCV structural proteins inducing immune suppression in the early phase of HCV infection contributed to the viral persistence, of which the activation of Treg cells might play an important role in the inhibition of an effective T cell antiviral response.https://www.mdpi.com/1999-4915/15/5/1082chimeric HCVinfection outcomeearly phase infectionimmune mechanismmarmoset model |
| spellingShingle | Bochao Liu Enhui Zhang Xiaorui Ma Shengxue Luo Chong Wang Ling Zhang Wenjing Wang Yongshui Fu Jean-Pierre Allain Chengyao Li Tingting Li Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in Marmosets Viruses chimeric HCV infection outcome early phase infection immune mechanism marmoset model |
| title | Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in Marmosets |
| title_full | Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in Marmosets |
| title_fullStr | Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in Marmosets |
| title_full_unstemmed | Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in Marmosets |
| title_short | Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in Marmosets |
| title_sort | early phase of specific cellular immune status associates with hcv infection outcomes in marmosets |
| topic | chimeric HCV infection outcome early phase infection immune mechanism marmoset model |
| url | https://www.mdpi.com/1999-4915/15/5/1082 |
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