Use this URL to cite or link to this record in EThOS:
Title: Modelling hepatitis C viral host interaction and co-infection
Author: Lissauer, Samantha Mary
ISNI:       0000 0004 7653 4260
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2018
Availability of Full Text:
Access from EThOS:
Access from Institution:
Hepatitis C Virus (HCV) is a clinically important infection that leads to chronic liver disease and Human Immunodeficiency Virus (HIV) co-infected patients have more rapid progression to severe liver disease and show higher rates of HCV vertical transmission. Hepatocytes are a highly differentiated cell type and support low level HCV replication. Most studies of the viral life cycle use de-differentiated hepatoma cell lines, which are highly permissive. The mechanism behind this difference is poorly understood. We show that dimethylsulfoxide (DMSO) differentiated Huh-7 cells have a 100-fold reduction in permissivity to HCV infection. We confirm that these cells are differentiated and upregulate key liver specific markers including miR122. They are metabolically active and have intact innate signaling pathways in response to infection. We observed a 10-fold reduction in the initiation of replication and a 10-fold loss in extra-cellular particle infectivity. In contrast cell-to-cell dissemination rates were comparable and cell-contact dependent infection of differentiated cells can overcome the restrictions seen in cell-free infection. HCV cell-to-cell transmission can also be mediated by other cell types. T cells are the primary cell supporting HIV-1 infection. We have shown that HCV can bind primary and immortalized T cells and trans-infect hepatoma cells. This requires replicating HIV but is independent of co-receptor engagement. HIV-1 infection of CD4+ T cells induces a significant increase in HCV trans-infection by increased viral binding. T cells provide a vehicle for HIV-1 to promote HCV infectivity, transmission and persistence.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR180 Immunology ; QR355 Virology