Abstract
Human hepatitis D virus (HDV) depends on hepatitis B virus co-infection and its glycoproteins for infectious particle formation. HDV was the sole known deltavirus for decades and believed to be a human-only pathogen. However, since 2018, several groups reported finding HDV-like agents from various hosts but without co-infecting hepadnaviruses. In vitro systems enabling helper virus-independent replication are key for studying the newly discovered deltaviruses. Others and we have successfully used constructs containing multimers of the deltavirus genome for the replication of various deltaviruses via transfection in cell culture. Here, we report the establishment of deltavirus infectious clones with 1.2× genome inserts bearing two copies of the genomic and antigenomic ribozymes. We used Swiss snake colony virus 1 as the model to compare the ability of the previously reported “2× genome” and the “1.2× genome” infectious clones to initiate replication in cell culture. Using immunofluorescence, qRT-PCR, immuno- and northern blotting, we found the 2× and 1.2× genome clones to similarly initiate deltavirus replication in vitro and both induced a persistent infection of snake cells. The 1.2× genome constructs enable easier introduction of modifications required for studying deltavirus replication and cellular interactions.
Highlights
Hepatitis D virus (HDV) is a unique human pathogen
We showed in a transfection-based assay that a plasmid bearing the SwSCV-1 genome in duplicate could initiate SwSCV-1 replication in cell culture, with highest efficacy observed in boid kidney cells [17]
Co-incidentally, Perez-Vargas and colleagues showed that hepatitis D virus (HDV) is able to use helper viruses other than HBV to form infectious particles [16]
Summary
Hepatitis D virus (HDV) is a unique human pathogen. Three years after its discovery in 1977 in liver specimens of chronically hepatitis B (HBV)-infected patients [1], Rizzetto and colleagues identified it as a satellite virus of HBV [2]. One can contract HDV in two different ways, either through acute co-infection with HBV or through superinfection as a chronic HBV carrier. Superinfection of a chronic HBV carrier by HDV results in the most severe form of viral hepatitis; these patients often face hepatic cirrhosis and development of hepatocellular carcinoma [3]. HDV is a satellite virus that utilizes the envelope proteins of HBV to assemble infectious viral particles; the replication of HDV within the host cell proceeds independently of HBV [4]. HDV gives rise to three different RNA species: the genome, the antigenome, and the mRNA. The host cell’s RNA polymerases mediate the replication of the HDV genome, which occurs via a double rolling circle mechanism [11]. The ribozymes cut the multimeric HDV RNA species produced during the rolling circle replication into unit-length pieces [11]
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