Interactions of human immunodeficiency virus type 1 with mucosal epithelial surfaces and Candida albicans

Despite the magnitude of the HIV pandemic, the events involved in the initial HIV-1 entry into the body are not yet fully understood. Although the principle mode of HIV-1 transmission is through mucosal surfaces, the oral epithelium appears to be less susceptible to HIV-1 infection than vaginal epithelium. In addition, infections with co-pathogens that elicit immune activation, such as Candida albicans, may also promote HIV-1 infection. The project objectives are to determine whether (i) HIV-1 is able to bind and integrate into oral and vaginal epithelial cell lines, (ii) epithelial cell lines are able to transfer viable virus from their surface to permissive cells, (iii) epithelial cells are responding to HIV-1 with changes in intracellular signalling or gene expression profiling, and (iv) Candida albicans can affect epithelial susceptibility to HIV-1 or whether it can bind and/or transfer HIV-1 to permissive cells. We demonstrate that oral, oro-pharyngeal and vaginal epithelial cell lines do not express canonical receptors for HIV-1 but they do express other receptors known to promote HIV-1 binding, including GalCer and syndecan-1. Oral and vaginal epithelial cell models can capture HIV-1, which subsequently does not appear to integrate into the epithelial genome. Therefore, viral replication is not supported. Notably, HIV-1 captured on the epithelial surface remains infectious and can be transferred to permissive cells. Furthermore, like epithelial cell lines, C. albicans can also directly bind and transfer HIV-1 to permissive cells. The carbohydrate moieties chitin and (3-glucan appear to play a role in mediating viral binding. Notably, transfer of HIV-1 to permissive cells occurs from chitin but minimally from p-glucan. This indicates that fungal-viral interactions may occur at mucosal surfaces that potentially promote HIV-1 infection.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2012

Author dc:creator

• Islam, Ayesha

Advisors dc:contributor.advisor

• Naglik, Julian Richard
• Challacombe, Stephen James

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/c8f83c82-f3af-469e-9790-8626f4b96d0f

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/c8f83c82-f3af-469e-9790-8626f4b96d0f