eprintid: 34251
rev_number: 16
eprint_status: archive
userid: 7870
dir: disk0/00/03/42/51
datestamp: 2024-01-12 07:42:58
lastmod: 2024-01-30 09:20:51
status_changed: 2024-01-12 07:42:58
type: doctoralThesis
metadata_visibility: show
creators_name: Schnell, Anna-Clara
title: Virus Venetian Masked Ball: Does the Hepatitis Delta Virus Use Different Helper Viruses?
subjects: ddc-570
divisions: i-140001
divisions: i-911700
adv_faculty: af-14
abstract: Changes in viral host cell tropism by e.g. changing receptor usage can lead to altered
disease manifestations, requiring different treatment modalities. Hepatitis Delta virus
(HDV), a small hepatotropic RNA virus, is known to depend on hepatitis B virus (HBV)
envelope proteins for envelopment and spread. However, as HDV possesses the ability
to replicate in non-hepatic cells and since envelopment of HDV was recently proposed to
be mediated by non-HBV viruses, there might be an increased potential for altered host
cell tropism of HDV due to differential envelope protein usage. This would have major
clinical implications, as currently only HBV positive carriers are screened for HDV and
specific therapeutic options only target HBV-dependent spread.
Viruses that were proposed to mediate envelopment of HDV include hepatitis C virus
(HCV) and vesicular stomatitis virus (VSV). As HDV is known for its liver tropism, I
focused primarily on hepatitis C virus (HCV) as potential HBV-independent helper and
aimed to evaluate the following questions: a) Does HDV make use of HCV envelope proteins? b) Can HDV be rendered susceptible for alternative helper usage by modification
of HBV specificity determinants in HDV? c) What is the zoonotic potential of HDV via
utilisation of non-human hepadnaviral helper viruses?
I made use of different human cell culture systems based on RNA transfection or viral
infection. Thereby, I was able to show efficient co-replication and co-infection of HDV
and HCV in the same cell. However, production of HCV enveloped HDV particles was
not observed. Based on plasmid transfection, I showed that HDV preferentially uses
HBV with little, if any, envelopment by HCV or VSV. Based on sequence comparison
to an animal Delta-like agent putatively using HBV-independent spread, I hypothesised
that determinants specifically targeting the HBV envelope might hinder HDV from using alternative viral envelopes. However, eliminating HBV specificity determinants from
HDV did not render HDV competent to use non-HBV envelopes. As the HDV-HBV
interaction is mediated by a tryptophan-rich domain on HBV envelope proteins, I examined HCV and VSV envelope proteins for the presence of similar determinants. However,
algorithm-based protein structure prediction did not detect such determinants, which is
consistent with the almost exclusive envelopment of HDV by HBV. Last, I investigated
various non-human hepadnaviruses for their capacity to provide helper function for HDV.
To this end, I produced non-infectious self-assembling particles exclusively consisting of
envelope proteins and preliminarily investigated secretion of HDV RNA mediated by
these particles.
Taken together, the data presented in this study support the current view that HDV
most likely utilises exclusively HBV as helper virus, further arguing for co-evolution of
these two viruses.
date: 2024
id_scheme: DOI
id_number: 10.11588/heidok.00034251
ppn_swb: 1879497840
own_urn: urn:nbn:de:bsz:16-heidok-342517
date_accepted: 2023-12-14
advisor: HASH(0x55e83b252a60)
language: eng
bibsort: SCHNELLANNVIRUSVENET20240110
full_text_status: public
place_of_pub: Heidelberg
citation:   Schnell, Anna-Clara  (2024) Virus Venetian Masked Ball: Does the Hepatitis Delta Virus Use Different Helper Viruses?  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/34251/1/PhDThesisSchnell.pdf