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Lymphotoxin-beta receptor activation in HBV-infected HepaRG cells

ABSTRACT: The objective of this experiment was to test the effect, at a transcrptomic level, of lymphotoxin-beta receptor activation in HBV-infected differentiated HepaRG cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE46667 | GEO | 2013/08/15

SECONDARY ACCESSION(S): PRJNA201437

REPOSITORIES: GEO

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Lymphotoxin-beta receptor activation in HBV-infected HepaRG cells

Project description:The objective of this experiment was to test the effect, at a transcrptomic level, of lymphotoxin-beta receptor activation in HBV-infected differentiated HepaRG cells 4 biological replicates per condition were analyzed

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Sera of individuals chronically infected with hepatitis B virus (HBV) contain diverse RNA types produced by HBV replication or derived from integrated HBV DNA

Project description:This study aimed to better characterize the repertoire of serum HBV RNAs during chronic HBV infection in humans, which remains understudied. Using RT-PCR, qPCR, RNA-sequencing and immuno-precipitation, we found that (i) >50% of serum samples bore different amounts of HBV replication-derived RNAs (rd-RNAs); (ii) a few samples contained RNAs transcribed from integrated HBV DNA including 5'-HBV-human-3' RNAs (integrant-derived RNAs or id-RNAs) and 5'-human-HBV-3' transcripts as a minority of serum HBV RNAs; (iii) spliced HBV RNAs were abundant in <50% of analyzed samples; (iv) most serum rd-RNAs were polyadenylated via conventional HBV polyadenylation signal; (v) pre-genomic RNA (pgRNA) was the major component of the pool of serum RNAs; (vi) area of HBV positions 1531-1739 had very high RNA reads coverage and thus should be used as a target for detecting serum HBV RNAs; (vii) vast majority of rd-RNAs and pgRNA were associated with HBV virions, but not with unenveloped capsids, exosomes, classic microvesicles or apoptotic vesicles and bodies; (viii) considerable rd-RNAs presence in the circulating immune complexes was found in a few samples; and (ix) serum rcDNA and rd-RNAs should be quantified simultaneously to evaluate HBV replication status and efficacy of anti-HBV therapy with nucleos(t)ide analogs. In summary, sera contain various HBV RNA types of different origin, which are likely secreted via different mechanisms. In addition, since we previously showed that id-RNAs were abundant or predominant HBV RNAs in many of liver and hepatocellular carcinoma tissues comparing to rd-RNAs, there is likely a mechanism favoring the egress of the replication-derived RNAs.

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