Michael P. Weekes
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View article: LRRC58 defines an E3 ubiquitin ligase complex sensitive to cysteine abundance
LRRC58 defines an E3 ubiquitin ligase complex sensitive to cysteine abundance Open
Adaptation to fluctuating nutrient supply is essential for organismal survival, but how cells sense and respond to changes in the abundance of many critical nutrients remains undefined. One such example is the amino acid cysteine, whose re…
View article: Virion proteomics of genetically intact HCMV reveals a regulator of envelope glycoprotein composition that protects against humoral immunity
Virion proteomics of genetically intact HCMV reveals a regulator of envelope glycoprotein composition that protects against humoral immunity Open
Human cytomegalovirus (HCMV) is a clinically important herpesvirus that has coevolved for millions of years with its human host, and establishes lifelong persistent infection. A substantial proportion of its 235 kb genome is dedicated to m…
Invasion preferences suggest a possible role for <i>Plasmodium falciparum</i> parasites in the expansion of Duffy negativity in West and Central Africa Open
Duffy antigen receptor for chemokines (DARC) is the primary red blood cell (RBC) receptor for invasion of human RBCs by Plasmodium vivax and knowlesi parasites. By contrast, Plasmodium falciparum parasites use multiple RBC receptors for in…
374 Time to Repair Flexor Tendon Injuries of the Hand and Its Association with Complications and Outcome Open
Aim The British Society for Surgery of the Hand (BSSH) recommends the operative management of open flexor tendon injuries of the hand should be undertaken within 4 days of injury and a functional range of active motion outcome at 3 months …
Dynamic subcellular proteomics identifies novel regulators of adipocyte insulin action Open
Insulin acts on adipocytes to suppress lipolysis and increase glucose uptake to control whole-body glucose and lipid metabolism. Regulation of these processes by insulin signalling depends on changes in protein localisation. However, the e…
View article: ISG15‐Dependent Stabilisation of USP18 Is Necessary but Not Sufficient to Regulate Type I Interferon Signalling in Humans
ISG15‐Dependent Stabilisation of USP18 Is Necessary but Not Sufficient to Regulate Type I Interferon Signalling in Humans Open
Type I interferon (IFN) signalling induces the expression of several hundred IFN‐stimulated genes (ISGs) that provide an unfavourable environment for viral replication. To prevent an overexuberant response and autoinflammatory disease, IFN…
Epstein–Barr virus BALF0/1 subverts the Caveolin and ERAD pathways to target B cell receptor complexes for degradation Open
Epstein–Barr virus (EBV) establishes persistent infection, causes infectious mononucleosis, is a major trigger for multiple sclerosis and contributes to multiple cancers. Yet, knowledge remains incomplete about how the virus remodels host …
View article: Virion Proteomics of Genetically Intact HCMV Reveals a Novel Regulator of Envelope Glycoprotein Composition that Protects Against Humoral Immunity
Virion Proteomics of Genetically Intact HCMV Reveals a Novel Regulator of Envelope Glycoprotein Composition that Protects Against Humoral Immunity Open
Human cytomegalovirus (HCMV) is a clinically important herpesvirus that has co-evolved for millions of years with its human host, and establishes lifelong persistent infection. A substantial proportion of its 235kb genome is dedicated to m…
Highly Multiplexed Proteomic Analysis of HCMV-Infected Dendritic Cells Reveals Global Manipulation of Adaptive Immunity and Host Restriction of Viral Replication Open
Human cytomegalovirus (HCMV) is a clinically significant herpesvirus and a paradigm for pathogen-mediated immune-evasion. Its broad tropism includes antigen-presenting cells such as dendritic cells (DCs), which may partly explain a unique,…
View article: HCMV US2 co-opts TRC8 to degrade the endoplasmic reticulum-resident protein LMAN2L
HCMV US2 co-opts TRC8 to degrade the endoplasmic reticulum-resident protein LMAN2L Open
The human cytomegalovirus (HCMV) pUS2 glycoprotein exploits the host’s endoplasmic reticulum (ER)-associated degradation (ERAD) pathway to degrade major histocompatibility complex class I (MHC-I) and prevent antigen presentation. Beyond MH…
Spatial proteomics identifies a novel CRTC-dependent viral sensing pathway that stimulates production of Interleukin-11 Open
Appropriate cellular recognition of viruses is essential for the generation of effective innate and adaptive antiviral immunity. Viral sensors and their signalling components thus provide a crucial first line of host defence. Many exhibit …
Epstein–Barr Virus BALF0/1 Subverts the Caveolin and ERAD Pathways to Target B-cell Receptor Complexes for Degradation Open
Epstein–Barr virus (EBV) establishes persistent infection, causes infectious mononucleosis, is a major trigger for multiple sclerosis and contributes to multiple cancers. Yet, knowledge remains incomplete about how the virus remodels host …
View article: Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection
Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection Open
Modified vaccinia Ankara (MVA) virus does not replicate in human cells and is the vaccine deployed to curb the current outbreak of mpox. Here, we conduct a multiplexed proteomic analysis to quantify >9000 cellular and ~80% of viral protein…
View article: Inhibition of human cytomegalovirus replication by interferon alpha can involve multiple anti-viral factors
Inhibition of human cytomegalovirus replication by interferon alpha can involve multiple anti-viral factors Open
The shortcomings of current direct-acting anti-viral therapy against human cytomegalovirus (HCMV) has led to interest in host-directed therapy. Here we re-examine the use of interferon proteins to inhibit HCMV replication utilizing both hi…
HCMV-secreted glycoprotein gpUL4 inhibits TRAIL-mediated apoptosis and NK cell activation Open
Human cytomegalovirus (HCMV) is a paradigm of pathogen immune evasion and sustains lifelong persistent infection in the face of exceptionally powerful host immune responses through the concerted action of multiple immune-evasins. These red…
ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways Open
Human cytomegalovirus (HCMV) is a major human pathogen whose life-long persistence is enabled by its remarkable capacity to systematically subvert host immune defenses. In exploring the finding that HCMV infection up-regulates tumor necros…
ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways Open
Human cytomegalovirus (HCMV) is a major human pathogen whose life-long persistence is enabled by its remarkable capacity to systematically subvert host immune defences. In exploring the finding that HCMV infection upregulates tumor necrosi…
View article: Strain-Dependent Restriction of Human Cytomegalovirus by Zinc Finger Antiviral Proteins
Strain-Dependent Restriction of Human Cytomegalovirus by Zinc Finger Antiviral Proteins Open
Determining the function of cellular antiviral factors can inform our understanding of virus replication. The zinc finger antiviral protein (ZAP) can inhibit the replication of diverse viruses.
Large-scale proteomic analysis of T. spiralis muscle-stage ESPs identifies a novel upstream motif for in silico prediction of secreted products Open
The Trichinella genus contains parasitic nematodes capable of infecting a wide range of hosts including mammals, birds and reptiles. Like other helminths, T. spiralis secretes a complex mixture of bioactive molecules capable of modulating …
Proteomic analysis of antiviral innate immunity Open
The capacity of host cells to detect and restrict an infecting virus rests on an array of cell-autonomous antiviral effectors and innate immune receptors that can trigger inflammatory processes at tissue and organismal levels. Dynamic chan…
View article: Human Cytomegalovirus Infection of Epithelial Cells Increases SARS-CoV-2 Superinfection by Upregulating the ACE2 Receptor
Human Cytomegalovirus Infection of Epithelial Cells Increases SARS-CoV-2 Superinfection by Upregulating the ACE2 Receptor Open
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused widespread morbidity and mortality since its onset in late 2019. Here, we demonstrate that prior infection…
View article: Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity
Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity Open
Summary Certain serum proteins, including CRP and D-dimer, have prognostic value in patients with SARS-CoV-2 infection. Nonetheless, these factors are non-specific, and provide limited mechanistic insight into the peripheral blood mononucl…
View article: Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study
Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study Open
Objective Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, soci…