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Extracellular HBV RNAs are heterogeneous in length and circulate as virions and capsid-antibody-complexes in chronic hepatitis B patients

Lu Bai, Xiaonan Zhang, Weixia Li, Min Wu, Jiangxia Liu, Maya Kozlowski, Liang Chen, Jiming Zhang, Yuxian Huang, Zhenghong Yuan
doi: https://doi.org/10.1101/320994
Lu Bai
aShanghai Public Health Clinical Center, Fudan University, Shanghai, China
bKey Laboratory of Medical Molecular Virology, Ministry of Education and Health, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China
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Xiaonan Zhang
aShanghai Public Health Clinical Center, Fudan University, Shanghai, China
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  • For correspondence: zhyuan@shaphc.org zhangxiaonan@shaphc.org
Weixia Li
aShanghai Public Health Clinical Center, Fudan University, Shanghai, China
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Min Wu
aShanghai Public Health Clinical Center, Fudan University, Shanghai, China
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Jiangxia Liu
bKey Laboratory of Medical Molecular Virology, Ministry of Education and Health, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China
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Maya Kozlowski
aShanghai Public Health Clinical Center, Fudan University, Shanghai, China
bKey Laboratory of Medical Molecular Virology, Ministry of Education and Health, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China
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Liang Chen
aShanghai Public Health Clinical Center, Fudan University, Shanghai, China
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Jiming Zhang
cDepartment of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
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Yuxian Huang
aShanghai Public Health Clinical Center, Fudan University, Shanghai, China
cDepartment of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
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Zhenghong Yuan
aShanghai Public Health Clinical Center, Fudan University, Shanghai, China
bKey Laboratory of Medical Molecular Virology, Ministry of Education and Health, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China
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  • For correspondence: zhyuan@shaphc.org zhangxiaonan@shaphc.org
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Abstract

Extracellular HBV RNA has been detected in both HBV-replicating cell culture media and sera from chronic hepatitis B (CHB) patients, but its exact origin and composition remain controversial. Here, we demonstrated that extracellular HBV RNA species were of heterogeneous lengths, ranging from the length of pregenomic RNA to a few hundred nucleotides. In cell models, these RNAs were predominantly associated with naked capsids although virions also harbored a minority of them. Moreover, HBV RNAs in hepatitis B patients’ blood circulation were localized in unenveloped capsids in the form of capsid-antibody-complexes (CACs) and in virions. Furthermore, we showed that extracellular HBV RNAs could serve as template for viral DNA synthesis. In conclusion, extracellular HBV RNAs mainly consist of pgRNA or the pgRNA species degraded by the RNase H domain of the polymerase in the process of viral DNA synthesis and circulate as CACs and virions. Their presence in the blood circulation of CHB patients may be exploited to develop novel biomarkers for HBV persistence.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted May 13, 2018.
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Extracellular HBV RNAs are heterogeneous in length and circulate as virions and capsid-antibody-complexes in chronic hepatitis B patients
Lu Bai, Xiaonan Zhang, Weixia Li, Min Wu, Jiangxia Liu, Maya Kozlowski, Liang Chen, Jiming Zhang, Yuxian Huang, Zhenghong Yuan
bioRxiv 320994; doi: https://doi.org/10.1101/320994
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Extracellular HBV RNAs are heterogeneous in length and circulate as virions and capsid-antibody-complexes in chronic hepatitis B patients
Lu Bai, Xiaonan Zhang, Weixia Li, Min Wu, Jiangxia Liu, Maya Kozlowski, Liang Chen, Jiming Zhang, Yuxian Huang, Zhenghong Yuan
bioRxiv 320994; doi: https://doi.org/10.1101/320994

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