The tetraspanin CD81 dynamics: investigating the role in hepatitis C virus entry

Barnes, Amy (2015). The tetraspanin CD81 dynamics: investigating the role in hepatitis C virus entry. University of Birmingham. Ph.D.

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Abstract

Hepatitis C Virus (HCV) infects hepatocytes, a liver cell type with complex polarity. Virus entry is a multi-step process that is dependent on a number of host proteins including CD81, scavenger receptor BI, and the tight junction proteins claudin-1 and occludin. CD81 is an attachment receptor for the virus, however, internalization is dependent upon CD81 association with claudin-1 to form a coreceptor complex.

The presentation and diffusion kinetics of CD81 shows variable conformation between diverse cell types. Using live imaging I show that CD81 diffusion is regulated by cellular localisation and polarity. Whilst the addition of growth factors and cytokines can modulate infection these effects are not consistently reflected by changes in CD81 diffusion, suggesting that CD81 diffusion kinetics alone does not define HCV entry. I demonstrate that the diffusion of the claudin-1 co-receptor also plays a role in defining infection. In addition, I demonstrate a complex interplay between the coreceptors and EGFR signalling that may involve the rearrangement of membrane domains to promote virus entry.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):