Extracellular Hepatitis B Virus RNAs Are Heterogeneous in Length and Circulate as Capsid-Antibody Complexes in Addition to Virions in Chronic Hepatitis B Patients

Abstract

Although increasing evidence suggests the presence of extracellular HBV RNA species, their origin and molecular forms are still under debate. In addition to the infectious virions, HBV is known to secrete several species of incomplete viral particles, including hepatitis B surface antigen (HBsAg) particles, naked capsids, and empty virions, during its replication cycle. Here, we demonstrated that extracellular HBV RNAs were associated with naked capsids and virions in HepAD38 cells. Interestingly, we found that unenveloped capsids circulate in the blood of hepatitis B patients in the form of CACs and, together with virions, serve as vehicles carrying these RNA molecules. Moreover, extracellular HBV RNAs are heterogeneous in length and represent either pregenomic RNA (pgRNA) or products of incomplete reverse transcription during viral replication. These findings provide a conceptual basis for further application of extracellular RNA species as novel biomarkers for HBV persistence.

Hepatitis B core-specific memory B cell responses associate with clinical parameters in patients with chronic HBV

“…Recently, antibody-HBV capsid complexes have been found in sera of patients with CHB. 21 Whether these capsids are actively secreted or released during cell-lysis or hepatocyte turnover remains to be determined. Besides differences in release of both antigens, localization in the infected liver might also contribute to the observed difference in B cell responses.…”

Biogenesis and molecular characteristics of serum hepatitis B virus RNA

“…However, it did not rule out the contamination from naked capsids, which contain all types of HBV replicative intermediates [4,7]. In line with this, another study showed that the extracellular HBV RNA are predominantly associated with naked capsids in cell cultures, but exist in capsid immunocomplexes and virions in patient sera [8]. Thus, the physical presence of serum HBV RNA remains to be defined.…”

Study on the structure optimization and anti‐hepatitis B virus activity of novel human La protein inhibitor HBSC11

“…On the contrary, the intracellular viral RNA level was increased upon ETV treatment (Figure C). Similarly, HBV DNA synthesis was significantly inhibited, whereas viral RNA was increased . The antigen inhibitory efficiency of compounds was assessed by ELISA.…”

“…Similarly, HBV DNA synthesis was significantly inhibited, whereas viral RNA was increased. 21 The antigen inhibitory efficiency of compounds was assessed by ELISA. As shown in Figures 4D,E, compound 5a and HBSC11 showed similar effect compared with ETV in reducing the antigen levels (approximately 50%).…”