Mark R. Wills
University of Cambridge
Cytotoxic T cellVirologyImmunologyHuman cytomegalovirusBiology
What is this?
Publications 92
HCMV infection, reinfection or reactivation occurs in 60% of untreated solid organ transplant (SOT) recipients. Current clinical approaches to HCMV management include pre-emptive and prophylactic antiviral treatment strategies. The introduction of immune monitoring to better stratify patients at risk of viraemia and HCMV mediated disease could improve clinical management. Current approaches quantify T cell IFNγ responses specific for predominantly IE and pp65 proteins ex vivo, as a proxy for fun...
#1Sarah E. JacksonH-Index: 18
#1Eleanor Y. Lim (University of Cambridge)H-Index: 1
view all 3 authors...
While CD8+ T cells specific for human cytomegalovirus (HCMV) have been extensively studied in both healthy HCMV seropositive carriers and patients undergoing immunosuppression, studies on the CD4+ T cell response to HCMV had lagged behind. However, over the last few years there has been a significant advance in our understanding of the importance and contribution that CMV-specific CD4+ T cells make, not only to anti-viral immunity but also in the potential maintenance of latently infected cells....
#1Timo W.M. De Groof (VU: VU University Amsterdam)H-Index: 2
#2Elizabeth Elder (University of Cambridge)H-Index: 1
Last. Martine J. Smit (VU: VU University Amsterdam)H-Index: 47
view all 7 authors...
Latent reservoirs of viral pathogens are significant barriers to eradication of these viruses. During latency, herpesviruses maintain their genome, with little gene expression, making latent infections refractory to current treatments targeting viral replication. In the case of human cytomegalovirus (HCMV), sporadic reactivation events are well controlled by the immune system. However, in immunocompromised or immunosuppressed individuals, HCMV reactivation often results in morbidity in solid org...
#1Rebecca Mason (UCL: University College London)
#2Ian J. Groves (University of Cambridge)H-Index: 11
Last. Matthew B. Reeves (UCL: University College London)H-Index: 23
view all 5 authors...
Human cytomegalovirus latency and reactivation is a major source of morbidity in immune-suppressed patient populations. Lifelong latent infections are established in CD34+progenitor cells in the bone marrow, which are hallmarked by a lack of major lytic gene expression, genome replication and virus production. A number of studies have shown that inhibition of the major immediate early promoter (MIEP) – the promoter that regulates immediate early (IE) gene expression – is important for the establ...
Human cytomegalovirus (HCMV) is the most frequent viral cause of congenital defects and can trigger devastating disease in immune-suppressed patients. Cytotoxic lymphocytes (CD8+ T cells and NK cells) control HCMV infection by releasing interferon-γ and five granzymes (GrA, GrB, GrH, GrK, GrM), which are believed to kill infected host cells through cleavage of intracellular death substrates. However, it has recently been demonstrated that the in vivo killing capacity of cytotoxic T cells is limi...
#1Janko Nikolich-Žugich (UA: University of Arizona)H-Index: 20
#2Luka Cicin-Sain (MHH: Hannover Medical School)H-Index: 21
Last. Niels Aw Lemmermann (University of Mainz)
view all 9 authors...
Cytomegalovirus (CMV) is one of the largest and most ubiquitous latent persistent viruses. Most humans are infected with CMV early in life, and all immunocompetent humans spend several decades living with CMV. In the vast majority of the hosts, CMV does not cause manifest disease, and CMV therefore can be considered part of normal aging for 50–90% of the human population worldwide. Experimental, clinical, and epidemiological studies suggest that CMV carriage can have nuanced outcomes, including ...
1 CitationsSource
#1Sarah Fidler (Imperial College London)H-Index: 32
#2Wolfgang Stöhr (UCL: University College London)H-Index: 19
Last. Mark Nelson (Imperial College London)H-Index: 65
view all 101 authors...
Summary Background Antiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing—termed kick and kill regimens—have been explored as a strategy towards an HIV cure. RIVER is the first randomised trial to determine the effect of ART-only versus ART plus kick and kill on markers of the HIV reservoir. Methods This phase 2, open-label, multicentre, rando...
5 CitationsSource
#1Fanny SalascH-Index: 1
#2David W. GludishH-Index: 7
Last. Hoi-Ping MokH-Index: 2
view all 8 authors...
#1Fanny Salasc (University of Cambridge)H-Index: 1
#2David W. Gludish (Cornell University)H-Index: 7
Last. Hoi-Ping Mok (University of Cambridge)H-Index: 2
view all 8 authors...
National Institutes for Health Research, UK (NIHR, Cambridge Biomedical Research Centres), the Cambridge Clinical Academic Reserve and the Medical Research Council, UK (MR/N02043X/1) . This work was also supported by the National Institute of Health (AI118582 and AI36097).
#1Elizabeth Elder (University of Cambridge)H-Index: 1
#2Benjamin Krishna (University of Cambridge)H-Index: 9
Last. John Sinclair (University of Cambridge)H-Index: 41
view all 10 authors...
ABSTRACT Human cytomegalovirus (HCMV) latency is an active process which remodels the latently infected cell to optimize latent carriage and reactivation. This is achieved, in part, through the expression of viral genes, including the G-protein-coupled receptor US28. Here, we use an unbiased proteomic screen to assess changes in host proteins induced by US28, revealing that interferon-inducible genes are downregulated by US28. We validate that major histocompatibility complex (MHC) class II and ...
6 CitationsSource