Institute of Immunity and Transplantation


HPV infections in X-SCID patients

Find out more about Dr Siobhan Burns' research on HPV infections in X-SCID patients.

We are working to understand the underlying molecular and cellular mechanisms that lead to primary immunodeficiency diseases. We have a particular focus on how defects in cells of the innate immune system contribute to immunodeficiencies we see in the clinic. As part of this research we are investigating the role of kerotinocyte defects in controlling HPV infection in individuals with X-SCID, through examining the common gamma chain.

The common gamma chain (gc: also known as interleukin-2 receptor subunit gamma, IL-2RG or CD132) is a componentheremultiple cytokine receptors. X-linked Severe Combined Immunodeficiency (X-SCID) is caused by loss of function mutations in gc
and is characterised by an absence of T and NK cells.

X-SCID is fatal unless treated with bone marrow transplantation or gene therapy in the first year of life. In two separate cohorts of SCID patients, adverse effects after bone marrow tranplantation decreased with the exception of severe cutaneous Human Papilloma Virus (HPV) infections.

Despite good immune reconstitution and restoration of T and NK cells, cutaneous HPV infection usually affects multiple affected sites and the warts are difficult to impossible to treat. As HPV infections are limited to the epidermis, we hypothesized that keratinocyte defects occur as part of X-SCID and remain after bone marrow transplantation.

To address this we have generated keratinocyte cell line models that lack yc following RNA silencing.

We are using organotypic rafts as a model to study keratinocyte differentiation in vitro and test HPV responses. Keratinocytes are seeded onto collagen rafts (seen in pink), then induced to differentiate on an air-liquid interface created using of cotton pads (white). Differentiated ‘skin’ forms on top of the collagen rafts within 14 days.

We are using these models to study the importance of keratinocyte-yc for controlling HPV infection.