The role of natural killer cells in control of varicella zoster virus infection

Varicella zoster virus (VZV) is a globally important virus with significant health and economic impacts. Although primary VZV infection is often perceived as a mild childhood illness, VZV infection is lifelong and reactivation of the latent virus in the elderly and immunocompromised population carries significant associated morbidity. Understanding precisely how the body responds to this virus is an important first step in tackling these challenges. As with other components of the innate response, Natural Killer (NK) cells respond directly to VZV infection, and VZV is likely to use evasion strategies to modulate the immune response. This thesis explores the details of this interplay between NK cells and VZV. First, I address the hypothesis that NK cell receptor expression in VZV seropositive patients is different to NK receptor expression in seronegative subjects. By comparing the expression of NK cell receptors in vivo in three cohorts of patients (seronegative, acutely infected, and recovered seropositive) I examine how these findings provide evidence to characterise the NK cell response to VZV, and to provide insight into viral mechanisms to evade detection by NK cells. Secondly, to address the hypothesis that specific ligand-receptor interactions between NK cells and infected cells responsible for control of VZV replication I examine changes in surface expression of NK cell ligands on infected cells in an vitro model of VZV infection using monocyte-derived dendritic cells (MDDC). Finally, using proteomic analysis, I explore changes in expression of proteins in in vitro infection in both monocyte-derived dendritic cells and an immortalised human keratinocytes cell line.

Name dc:type.qualificationname

Doctor of Medicine (MD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2022

Author dc:creator

• Allen, Caroline Patricia

Advisor dc:contributor.advisor

• Ogg, Graham

• Varicella zoster virus (VZV)
• Natural Killer (NK) cells
• Infection
• Immunity
• Ligands

Licence

• https://www.repository.cam.ac.uk/bitstreams/5835641c-09cc-4c9b-9f97-847239418a21/download
• https://creativecommons.org/licenses/by-nc-sa/4.0/

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.107340

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/366379