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Memorial University - Electronic Theses and Dissertations 2
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Document Description
TitleInvestigation of woodchuck hepatitis virus-cell interactions
AuthorDesousa, Jacques Real Barroso, 1964-
DescriptionThesis (M.Sc.)--Memorial University of Newfoundland, 1994. Medicine
Paginationxxi, 253 leaves : ill.
SubjectHepatitis B virus; Hepatitis B--Molecular aspects
Degree GrantorMemorial University of Newfoundland. Faculty of Medicine
NotesBibliography: leaves 219-253.
AbstractHepatitis B virus (HBV) is a highly hepatotropic DNA virus, which causes several life threatening liver diseases. These diseases are a major public health problem of worldwide proportions. Initial binding of HBV to host cells is poorly understood. However, virus attachment is an event of utmost importance because it determines viral species specificity and cell tropism and, in consequence, viral pathogenicity. Among hepadnaviruses, the woodchuck hepatitis virus (WHV) displays the highest degree of molecular and biological similarity to HBV. Pending the availability of applicable cell cultures, a woodchuck model of hepatitis B offers a valuable in vivo system for the study of hepadnaviral attachment. -- The aim of this thesis was to recognize the properties of WHV binding to the host cell surface. The studies revealed that the WHV envelope (WHsAg) binds to woodchuck hepatocyte plasma membranes (HPMs) with kinetics that suggest specific ligand-receptor interaction. Further, they also demonstrated that a 330-kD HPM molecule is involved in the virus attachment. Plasma membranes isolated from woodchuck splenocytes and kidney cells also bound WHsAg, however, to a lesser extent, when compared to HPMs. These non-hepatic membranes exhibited a similar 330-kD WHV binding molecule. Results obtained through virus and lectin affinity chromatography and enzymatic digestions revealed that the binding of the WHV envelope displayed by the 330-kD molecule is mediated both by N-linked polymannose and O-linked heparan sulphate, but not by the protein core which links these carbohydrates. This suggests that the 330-kD receptor is a proteoglycan and that its virus binding site is constituted both by heparan sulphate and by polymannose. Preincubation of the WHV envelope with an exogenous glycosaminoglycan, heparin, inhibited the binding of WHV envelope to the 330-kD receptor, as well as to host intact HPMs. This suggests that the WHV attachment may be blocked by heparin-like substances in vivo. -- The nature of the WHV envelope interaction with host cells was further investigated when a peptide homologous to the N-terminal sequence of the virus envelope preSl protein, predicted to be exposed at the virion surface, was synthesized and used to test its specificity towards species, cells and subcellular organelles. The peptide demonstrated specific binding to an intracellular component exclusively expressed in woodchuck hepatocytes and lymphoid cells, suggesting that an intracellular receptor molecule(s) may play a role in determining virus tropism.
Resource TypeElectronic thesis or dissertation
FormatImage/jpeg; Application/pdf
SourcePaper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries
Local Identifier76203927
RightsThe author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.
CollectionElectronic Theses and Dissertations
Scanning StatusCompleted
PDF File(27.23 MB) --
CONTENTdm file name97971.cpd