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 inter-ference 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 im-mune responses during coinfection,which renews the knowledge on the nature of indirect viral interaction during HBV/HCV coinfection.

Center for Biosafety Mega-Science,State Key Laboratory of Virology,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan,430071,China;University of Chinese Academy of Sciences,Beijing 100049,China;Division of Infectious Diseases,Department of Medicine,Icahn School of Medicine at Mount Sinai,New York,10029,USA;State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology,School of Basic Medical Sciences,Wuhan University,Wuhan,430071,China;Henan Mental Hospital,the Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453002,China;Joint Center of Translational Precision Medicine,Guangzhou Institute of Pediatrics,Guangzhou Women and Children Medical Center,Guangzhou,510623,China;Department of Thoracic Surgery,The Second Affiliated Hospital of Medical School,Xi'an Jiaotong University,Xi'an,710004,China;Department of Medicine,Icahn School of Medicine at Mount Sinai,New York,10029,USA;Department of Laboratory Medicine,Maternal and Child Health Hospital of Hubei Province,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430030,China;Institute of Virology,University Hospital Essen,University of Duisburg-Essen,Essen,45147,Germany;Guangzhou Laboratory,Guangzhou,510005,China

[1]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)[J].中国病毒学,2022(03):408-417

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