Enhanced host immune responses in presence of HCV facilitate HBV clearance in coinfection

Shuhui Liu; Kaitao Zhao; Xi Su; Xiaoxiao Gao; Yongxuan Yao; Ranran Kong; Yun Wang; Chunchen Wu; Mengji Lu; Xinwen Chen; Rongjuan Pei

doi:10.1016/j.virs.2022.04.001

June 2022

Shuhui Liu, Kaitao Zhao, Xi Su, Xiaoxiao Gao, Yongxuan Yao, Ranran Kong, Yun Wang, Chunchen Wu, Mengji Lu, Xinwen Chen and Rongjuan Pei. Enhanced host immune responses in presence of HCV facilitate HBV clearance in coinfection[J]. Virologica Sinica, 2022, 37(3): 408-417. doi: 10.1016/j.virs.2022.04.001

Citation: Shuhui Liu, Kaitao Zhao, Xi Su, Xiaoxiao Gao, Yongxuan Yao, Ranran Kong, Yun Wang, Chunchen Wu, Mengji Lu, Xinwen Chen, Rongjuan Pei. Enhanced host immune responses in presence of HCV facilitate HBV clearance in coinfection .VIROLOGICA SINICA, 2022, 37(3) : 408-417. http://dx.doi.org/10.1016/j.virs.2022.04.001

HCV通过增强宿主免疫反应促进共感染中HBV的清除

刘淑慧 ^a,b,g ,
赵凯涛 ^a,b,h ,
苏玺 ^a,b,i ,
高晓霄 ^a,b ,
姚永璇 ^a,b,j ,
孔冉冉 ^c,d ,
王云 ^a ,
吴春晨 ^a,k ,
陆蒙吉 ^e ,
陈新文 ^a,f ,
裴荣娟 ^a,,

中国科学院武汉病毒研究所

通讯作者： 裴荣娟, rongjuan_pei@wh.iov.cn
收稿日期： 2021-08-20
录用日期： 2022-03-21

摘要

由于共用相同的感染途径和宿主细胞，乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）共感染在临床上很常见。虽然在共感染病例中发现HBV和HCV存在相互抑制的现象，但不论是哪种病毒呈优势，共感染都被证实与疾病发展密切相关。目前，HBV/HCV共感染中病毒相互抑制的具体机制并不清楚。前期体外细胞实验证明，HBV与HCV基因组可以在同一细胞复制，但并不存在直接的相互抑制关系，这预示宿主体内病毒间的相互影响可能是由宿主免疫反应系统参与并介导的间接作用的结果。为了证实并揭示潜在的上述机制，我们在能自然感染HBV和HCV病毒颗粒的Huh7-NTCP细胞中和具有完整免疫系统的能自然感染HCV病毒颗粒的HCV受体转基因小鼠体内进行了HBV/HCV共感染。结果显示，HBV和HCV能感染同一个Huh7-NTCP细胞，并实现有效病毒复制。但与对照组相比，HCV能显著抑制HBV复制。体内共感染同样显示的结果，且HCV对HBV复制的抑制作用与两种病毒的感染先后顺序无关。而与HVCV单独感染组相比，不论是在体外细胞中还是小鼠体内，HBV对HCV复制均没有显著影响。小鼠血液生化和肝脏病理检测结果显示，共感染组在一定时间内呈现出更严重的病理进程，但随着HBV病毒的清除，病变得到恢复。对小鼠免疫反应进行检测发现，与HBV单独感染组相比，共感染组的天然免疫反应明显增强，而与HCV单独感染组相当。进一步检测适应性免疫反应显示，HCV的存在显著增强了小鼠体内HBV特异性体液和细胞免疫反应。由此可见，在HBV/HCV共感染过程中，HCV通过增强宿主的天然和适应性免疫反应抑制HBV复制，并促进HBV清除。
- 乙型肝炎病毒(HBV)
- , 丙型肝炎病毒(HCV)
- , 共感染
- , 天然免疫反应
- , 适应性免疫反应

Enhanced host immune responses in presence of HCV facilitate HBV clearance in coinfection

Shuhui Liu ^a,b,g ,
Kaitao Zhao ^a,b,h ,
Xi Su ^a,b,i ,
Xiaoxiao Gao ^a,b ,
Yongxuan Yao ^a,b,j ,
Ranran Kong ^c,d ,
Yun Wang ^a ,
Chunchen Wu ^a,k ,
Mengji Lu ^e ,
Xinwen Chen ^a,f ,
Rongjuan Pei ^a,,

a Center for Biosafety Mega-Science, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China;

Corresponding author: Rongjuan Pei, rongjuan_pei@wh.iov.cn
Received Date: 20 August 2021
Accepted Date: 21 March 2022

Abstract

Hepatitis B virus (HBV)/Hepatitis C virus (HCV) coinfection is frequently observed because of the common infection routine. Despite the reciprocal inhibition exerted by HBV and HCV genomes, the coinfection of HBV and HCV is associated with more severe forms of liver diseases. However, the complexity of viral interference and underlying pathological mechanism is still unclarified. With the demonstration of absence of direct viral interplay, some in vitro studies suggest the indirect effects of viral-host interaction on viral dominance outcome. Here, we comprehensively investigated the viral replication and host immune responses which might mediate the interference between viruses in HBV/HCV coinfected Huh7-NTCP cells and immunocompetent HCV human receptors transgenic ICR mice. We found that presence of HCV significantly inhibited HBV replication in vitro and in vivo irrespective of the coinfection order, while HBV did not affect HCV replication. Pathological alteration was coincidently reproduced in coinfected mice. In addition to the participation of innate immune response, an involvement of HCV in up-regulating HBV-specific immune responses was described to facilitate HBV clearance. Our systems partially recapitulate HBV/HCV coinfection and unveil the uncharacterized adaptive anti-viral immune responses during coinfection, which renews the knowledge on the nature of indirect viral interaction during HBV/HCV coinfection.
- Hepatitis B virus (HBV)
- , Hepatitis C virus (HCV)
- , Coinfection
- , Viral-host interaction
- , Immunocompetent mouse model

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