Show simple item record

FieldValueLanguage
dc.contributor.authorMachala, Emily Ann
dc.date.accessioned2019-08-01
dc.date.available2019-08-01
dc.date.issued2018-12-20
dc.identifier.urihttp://hdl.handle.net/2123/20834
dc.description.abstractHuman cytomegalovirus (HCMV) and Herpes Simplex Virus Type 1 (HSV-1) are double stranded DNA viruses of the herpesvirus family. Herpesviruses are ubiquitous pathogens that establish life-long latency with the potential to reactivate resulting in a range of diseases. In the absence of a licensed vaccine for either virus there remains a significant requirement for novel treatment strategies. Galectins are a family of cellular proteins characterised by the presence of a carbohydrate recognition domain that facilitates their lectin functionality. Members of this widely expressed protein family have been implicated in modulating both antiviral immunity and regulation of direct host-virus interactions. Previous studies from the Slobedman laboratory have established Galectin-9 (Gal-9) was potently upregulated by the antiviral cytokine IFN-β during HCMV infection. However, the potential for Gal-9 to directly modulate infection has not previously been studied in the context of any herpesvirus. Infection studies utilising recombinant protein treatment revealed Gal-9 as an antiviral lectin that inhibited both HCMV and HSV-1 infection. This inhibition of infection was consistent during infection of a range of clinically relevant cell types in a dose dependent manner. Further analysis established that Gal-9 mediated inhibition of infection could be blocked by anti- Gal-9 specific antibodies, and was carbohydrate recognition domain-dependent. Temperature-shift studies that separated the binding and fusion stages of viral entry identified Gal-9 specific inhibition as mediated primarily at the level of viral entry, and appeared to be dependent on binding to the virion rather than interacting with cellular ligands. This study provides the first evidence of a novel role for Gal-9 as an antiviral lectin that exerts a profound inhibitory effect on both HCMV and HSV-1 infection.en_AU
dc.publisherUniversity of Sydneyen_AU
dc.publisherFaculty of Medicine and Healthen_AU
dc.publisherSydney Medical Schoolen_AU
dc.publisherCentral Clinical Schoolen_AU
dc.rightsThe author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.en_AU
dc.subjecthuman cytomegalovirusen_AU
dc.subjectantiviralen_AU
dc.subjectgalectinen_AU
dc.subjectherpes simplex virusen_AU
dc.titleInvestigation of Galectin-9 as an Antiviral Lectin During Human Cytomegalovirus and Herpes Simplex Virus Type 1 Infectionsen_AU
dc.typePhD Doctorateen_AU
dc.type.pubtypeDoctor of Philosophy Ph.D.en_AU
dc.description.disclaimerAccess is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.en_AU


Show simple item record

Associated file/s

Associated collections

Show simple item record

There are no previous versions of the item available.