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Mechanisms of HHV-8 (KSHV) pathogenesis in post-renal transplant Kaposi sarcoma: Viral and host factors and the role of immunosuppressive regimens

Code: BC-DTP_2026_67

Title: Mechanisms of HHV-8 (KSHV) pathogenesis in post-renal transplant Kaposi sarcoma: Viral  and host factors and the role of immunosuppressive regimens

Primary Supervisor: Catherine Harwood

Email: c.a.harwood@qmul.ac.uk

Institute: Blizard Institute

Secondary Supervisor: Teresa Cutino-Moguel

Email: maria-teresa.cutino-moguel@nhs.net

Institute: National Health Service (NHS)

Lay Summary:

HHV-8 is a virus that does not usually cause disease in people with normal immune systems. It is more common in certain areas such as sub Saharan Africa (SSA) and in people living with HIV (PLWH). When it infects people with reduced immune systems, including  kidney transplant recipients (KTRs), some develop  Kaposi sarcoma (KS), a type of cancer which can cause a transplant failure, significant health problems and death. In East London more KTRs are developing KS, mainly because more KTRs are from SSA or are PLWH and so already infected with HHV-8, but occasionally because the kidney donor was infected.  We do not know how best to identify people at risk, nor do we fully understand the role their transplant anti-rejection drugs play. This study investigates why only some some KTRs with HHV-8 develop KS. In the clinic we will find out the prevalence of HHV-8 in kidney donors and recipients, particularly in those from countries where HHV-8 is common. We will measure HHV-8 DNA in blood over time after transplant and see if it correlates with KS. In the lab we will infect artificial cell lines with HHV-8 to understand what genes are activated in patients with KS and compare it to those that had HHV-8 but did not develop KS. Finally we will investigate how anti-rejection drugs interact with HHV-8 to cause KS. This research  will allow us to better identify KTRs at risk of KS and offer these patients safer anti-rejection medication to reduce this risk.

Aims:

The aim of this study is to identify OTRs risk of developing KS and to understand how viral factors and the host immune response contribute to that risk. The ultimate aim is the identification of therapeutic targets and improved management and outcomes for SOTs  with KS.

Primary objectives

  1. To characterize:
  2. HHV-8 infection serostatus in our kidney donor and recipient population
  3. HHV-8 DNA viral load and antibody kinetics in seropositive donors and recipients in relation to onset of KS
  4. HHV-8 viral gene expression in KTRs who develop KS versus matched seropositive controls without KS.
  5. To determine how common immunosuppressive drugs (cyclosporine, tacrolimus, mycophenolate, sirolimus) affect HHV-8 latency/lytic reactivation and endothelial cell transformation in vitro.
  6. To identify host signaling pathways and cytokine signatures (eg. mTOR, VEGF, IL-6 family) modulated by viral infection and by immunosuppressants to propose drugable therapeutic targets
  7. To test novel antiviral molecules based on cyclosporine with collaborators (David Selwood, medical chemistry) and Greg Towers (molecular virology)
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