Viral infection following stem cell transplantation (SCT) is a common complication following this procedure which is performed for the treatment of blood cancers. One such pathogen is respiratory syncytial virus (RSV), a common community-acquired infection that leads to significant morbidity in immunocompromised patients such as recipients of a SCT. Current treatment strategies using anti-viral agents are ineffective and thus this complication remains a significant clinical problem where new treatments are desperately needed. To address this, a better understanding of the immunological mechanisms which underlie this complication are essential. We have published extensively using pre-clinical models of stem cell transplantation. The specific aim of this project is to establish a model of RSV infection in the stem cell transplant setting using Pneumonia Virus of Mice (PVM), the murine relative of RSV. The contribution of host innate and acquired mucosal immune responses to the viral infection will be dissected. In addition, the direct pathogenic role of the virus will be examined. This project is not limited to, but will involve, extensive animal work, flow cytometry and immunological assays, and is best suited for a PhD candidate.
Dr Varelias’ Selected Key Publications:
1. Varelias A*, Bunting MD*, Ormerod KL, Koyama M, Olver SD, Straube J, Kuns RD, Robb RJ, Henden AS, Cooper L, Lachner N, Gartlan KH, Lantz O, Kjer-Nielsen L, Mak JYW, Fairlie DP, Clouston AD, McCluskey J, Rossjohn J, Lane SW, Hugenholtz P and Hill GR. Recipient Mucosal-Associated Invariant T Cells control GVHD within the colon. J Clin Invest. 128(5):1919-1936 (2018). *Joint first authors.
2. Varelias A, Ormerod KL, Bunting MD, Koyama M, Gartlan KH, Kuns RD, Lachner N, Locke KR, Lim CY, Henden AS, Zhang P, Clouston AD, Hasnain SZ, McGuckin MA, Bruce R Blazar, MacDonald KPA, Hugenholtz P and Hill GR. Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome. Blood. 129(15):2172-2185 (2017).
3. Varelias A, Gartlan KH, Kreijveld E, Olver SD, Lor M, Kuns RD, Lineburg KE, Teal BE, Raffelt N, Cheong M, Alexander KA, Koyama M, Markey KA, Sturgeon E, Leach J, Reddy P, Kennedy GA,
Yanik G, Blazar BR, Tey S-K, Clouston AD, MacDonald KPA, Cooke KR and Hill GR. Lung parenchyma–derived IL-6 promotes IL-17A–dependent acute lung injury after allogeneic stem cell
transplantation. Blood. 125(15):2435-44 (2015).
4. Kennedy GA*, Varelias A*, Vuckovic S, Le Texier L, Gartlan KH, Zhang P, Thomas G, Anderson L, Boyle G, Cloonan N, Leach J, Sturgeon E, Avery J, Olver SD, Lor M, Misra AK, Hutchins C, Morton AJ, Durrant STS, Subramoniapillai E, Butler JP, Curley CI, MacDonald KPA, Tey SK and Hill GR.
Addition of IL-6 inhibition to standard GVHD prophylaxis after allogeneic stem cell transplantation: a phase I/II trial. Lancet Oncol. 15(13):1451-9 (2014). *Joint first authors.
5. Koyama M, Kuns RD, Olver SD, Raffelt NC, Wilson YA, Don AL, Lineburg KE, Cheong M, Robb RJ, Markey KA, Varelias A, Malissen B, Hämmerling GJ, Clouston AD, Engwerda CR, Bhat P,
MacDonald KP and Hill GR. Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease. Nat Med. 18(1):135-42 (2012).