Host-pathogen interactions, and Cytomegalovirus latency and pathogenesis.
Human Cytomegalovirus (HCMV) remains a major clinical complication in a number of settings including immune-suppressed transplant patients and following congenital infection. The ability of HCMV, like all herpes viruses, to establish a lifelong latent infection of the host results in the threat posed by HCMV as twofold: Transplant patients are at risk following primary infection or following the reactivation of the latent virus that resides in the recipient.
Our group is part of the CMV research group (with Prof Griffiths) and is focussed on dissecting the molecular basis of HCMV latency and reactivation as well as the role of host cell functions during lytic infection. Specifically, we are investigating the contribution of both viral and cellular functions to the maintenance of latency with particular emphasis on how cell signalling pathways are important during both the establishment and reactivation of the latent infection.
Alongside these studies we investigate the natural history of HCMV in solid organ transplant patients. Here the focus is to understand the role of viral genetics and host immunity in the onset of viraemia in these patients with a view to a clearer understanding of why certain individuals are at increased risk of HCMV pathogenesis.
- Selected publications
- Poole EL, Lau JCH, Murray MJ, Kew VG, Stamminger T, Sinclair JH, Reeves MB. A virally dependent de-sumoylase activity is required for HCMV reactivation from latency. Cell Reports. 2018. Accepted.
- Baraniak I, Kropff B, Ambrose L, McIntosh M, McLean GR, Pichon S, Atkinson C, Milne RSB, Mach M, Griffiths PD, Reeves MB. Protection from cytomegalovirus viremia following glycoprotein B vaccination is not dependent on neutralizing antibodies. Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):6273-6278. doi:10.1073/pnas.1800224115. Epub 2018 Apr 23. PubMed PMID: 29686064; PubMed Central PMCID: PMC6004462.
- Murray MJ, Peters NE, Reeves MB. Navigating the host cell response during entry into sites of latent cytomegalovirus infection Pathogens. 2018;7:pii:E30
- Baraniak I, Kropff B, McLean GR, Pichon S, Piras-Douce F, Milne RSB, Smith C, Mach M, Griffiths PD, Reeves MB. Epitope-Specific Humoral Responses to Human Cytomegalovirus Glycoprotein-B Vaccine with MF59: Anti-AD2 Levels Correlate with Protection from Viremia. J Infect Dis. 2018 [Epub ahead of print]
- Kew VG, Wills MR, Reeves MB. LPS promotes a monocyte phenotype permissive for human cytomegalovirus immediate-early gene expression upon infection but not reactivation from latency. Sci. Rep. 2017;7:810
- Dupont L, Reeves MB. Cytomegalovirus latency and reactivation: recent insights into an age old problem. Rev Med Virol. 2016;26:75-89
- Kew VG, Yuan J, Meier J, Reeves MB. Mitogen and stress activated kinases act co-operatively with CREB during the induction of human cytomegalovirus immediate-early gene expression from latency. PLoS Pathog. 2014;10:e1004195
- Reeves MB, Sinclair JH. Circulating dendritic cells isolated from healthy seropositive donors are sites of human cytomegalovirus reactivation in vivo. J Virol. 2013;87:10660-7
- Huang MM, Kew VG, Jestice K, Wills MR, Reeves MB. Efficient human cytomegalovirus reactivation is maturation dependent in the Langerhans dendritic cell lineage and can be studied using a CD14+ experimental latency model. J Virol. 2012;86:8507-15
- Reeves MB, Breidenstein A, Compton T. Human cytomegalovirus activation of ERK and myeloid cell leukaemia-1 protein correlates with survival of latently infected cells. PNAS. 2012;109:588-93
- Reeves MB, Davies AA, McSharry BP, Wilkinson GW, Sinclair JH. Complex I binding by a virally encoded RNA regulates mitochondria-induced cell death. Science. 2007;316:1345-8 (see also Perspectives section in Science 317:329-30)
- Reeves MB, MacAry PA, Lehner PJ, Sissons JGP, Sinclair JH. Latency, chromatin remodelling and reactivation of HCMV in the dendritic cells of healthy carriers. PNAS. 2005;102:4140-5.
- View all publications
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