The heterogeneous ribonuclear protein C interacts with the hepatitis delta virus small antigen

Abstract

BackgroundHepatitis delta virus (HDV) is considered to be a satellite virus of the Hepatitis B virus. The genome consists of a 1679 nt ssRNA molecule in which a single ORF was identified. This ORF codes for a unique protein, the Delta antigen (HDAg). During transcription, two forms, small (S-HDAg; p24) and large (L-HDAg; p27) of this antigen are derived as a result of an editing mechanism catalyzed by cellular adenosine deaminase 1. Despite its simplicity, little is still known about the host factors that interact with the virus RNA and antigens being to modulate virus replication.MethodsA yeast two-hybrid screening of a human liver cDNA library, using the hepatitis delta virus (HDV) small antigen (S-HDAg) as bait, was performed. Blot overlay and co-immunoprecipitation assays were used in an attempt to confirm the interaction of hnRNPC and S-HDAg. siRNA knockdown assays of hnRNPC were performed to assess the effect on HDV antigen expression.ResultsThirty known proteins were identified as S-HDAg interactors in the yeast two-hybrid screening. One of the identified proteins, hnRNPC, was found to interact with S-HDAg in vitro and in vivo in human liver cells. The interaction of the two proteins is mediated by the C-terminal half of the S-HDAg which contains a RNA-binding domain (aa 98-195). HDV RNA, S-HDAg, and hnRNPC, were also found to co-localize in the nucleus of human liver cells. Knockdown of hnRNPC mRNA using siRNAs resulted in a marked decreased expression of HDV antigens.ConclusionsS-HDAg was found to interact with human liver proteins previously assigned to different functional categories. Among those involved in nucleic acid metabolism, hnRNPC was found to interact in vitro and in vivo in human liver cells. Similar to other RNA viruses, it seems plausible that hnRNPC may also be involved in HDV replication. However, further investigation is mandatory to clarify this question.

Hepatitis Delta Virus: A Peculiar Virus

“…This set included 9 of the 12 subunits of the pol II complex, further supporting the idea that pol II is involved in HDV RNA transcription [106]. In another study, a yeast two-hybrid approach identified 30 proteins encoded by a human liver cDNA library that interacted with S-HDAg [107]. Only three proteins from this study had also been identified by the previously mentioned immunopurification approach.…”

Prevalence and genotype distribution of hepatitis delta virus among chronic hepatitis B carriers in Central Vietnam

“…The HDV genome consists of approx. 1680 nucleotides covered by approximately 200 hepatitis D antigen molecules (HDAg) [ 2 , 9 ]. HDV needs the presence of HBV envelope proteins for its assembly, propagation, and transmission to initiate new rounds of infection [ 6 , 10 ].…”

N6-Methyladenosine RNA Methylation Regulators Have Clinical Prognostic Values in Hepatocellular Carcinoma

“…In addition, a high expression of HNRNPC has a poor prognosis and may act as a candidate biomarker for chemoresistance in gastric cancer ( Huang et al, 2016 ). Besides that, HNRNPC also acts as a dengue virus NS1-interacting protein and plays an important role during the replication of the hepatitis C virus and hepatitis delta virus ( Noisakran et al, 2008 ; Casaca et al, 2011 ). Our results imply that HNRNPC is a candidate biomarker for HCC.…”