Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in Marmosets.
Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in Marmosets.
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DOI：
10.3390/v15051082
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发表时间：
2023-04-28
期刊：
影响因子：
--
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Liu B;Zhang E;Ma X;Luo S;Wang C;Zhang L;Wang W;Fu Y;Allain JP;Li C;Li T
决定HCV感染结果的主要机制尚未完全描述，特别是在感染的“窗口期”的早期。本研究以HCV-CE 1 E2 p7/GBV-B嵌合病毒（HCV chimera）和GBV-B两组绒猴为研究对象，探讨病毒感染不同结局的免疫机制。将含有完整HCV核心和包膜蛋白（CE 1 E2 p7）和GBV-B RNA的HCV嵌合体分别肝内注射到每组中的4只绒猴中。每隔2周从个体动物中采集血样。在两组HCV嵌合体和GBV-B感染的绒猴中检测病毒载量和特异性T细胞应答。HCV嵌合体感染的绒猴似乎在病毒接种后6个月内具有病毒持续感染。其中，特异性IFN-γ分泌T细胞应答在13至19周内缓慢发展，并在40-70 SFC/106 PBMC下维持在相对低的水平，而特异性Treg细胞应答在3周内迅速活化，并在淋巴细胞中维持在约5%的高水平。相比之下，GBV-B感染的绒猴在6个月内表现出自发的病毒清除;特异性IFN-γ分泌T细胞应答在5至7周内迅速建立，并维持在50-130 SFC/106 PBMC的高水平，而特异性Treg细胞应答被灭活，并维持在淋巴细胞中低于3%的基线。结论：HCV感染早期诱导免疫抑制的HCV结构蛋白参与了病毒的持续存在，其中Treg细胞的激活可能在抑制有效的T细胞抗病毒反应中起重要作用。
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/106 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/106 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.
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影响因子：
6.7
作者：
Hasenkrug KJ;Chougnet CA;Dittmer U
通讯作者：
Dittmer U
影响因子：
5.9
作者：
Bandiera, Simonetta;Bian, C. Billie;Hoshida, Yujin;Baumert, Thomas F.;Zeisel, Mirjam B.
通讯作者：
Zeisel, Mirjam B.
影响因子：
4.8
作者：
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通讯作者：
Baldanti F
影响因子：
3.7
作者：
Bukh, J;Apgar, CL;Yanagi, M
通讯作者：
Yanagi, M
影响因子：
4.4
作者：
Suvas, S;Azkur, AK;Rouse, BT
通讯作者：
Rouse, BT