RT Journal Article
SR Electronic
T1 Extracellular HBV RNAs are heterogeneous in length and circulate as virions and capsid-antibody-complexes in chronic hepatitis B patients
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 320994
DO 10.1101/320994
A1 Lu Bai
A1 Xiaonan Zhang
A1 Weixia Li
A1 Min Wu
A1 Jiangxia Liu
A1 Maya Kozlowski
A1 Liang Chen
A1 Jiming Zhang
A1 Yuxian Huang
A1 Zhenghong Yuan
YR 2018
UL http://biorxiv.org/content/early/2018/05/13/320994.abstract
AB 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.