A5063356558- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Herpesvirus Infections and Treatments
- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Virus-based gene therapy research
- Toxoplasma gondii Research Studies
- interferon and immune responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immunotherapy and Immune Responses
- Polyomavirus and related diseases
- Galectins and Cancer Biology
- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Mycobacterium research and diagnosis
- RNA regulation and disease
- Bee Products Chemical Analysis
- Toxin Mechanisms and Immunotoxins
- Biosensors and Analytical Detection
- Systemic Sclerosis and Related Diseases
- Renal and related cancers
- Pneumocystis jirovecii pneumonia detection and treatment
- HIV Research and Treatment
- Single-cell and spatial transcriptomics
- Extracellular vesicles in disease
Westmead Institute
2009-2023
Westmead Institute for Medical Research
2019-2023
The University of Sydney
2013-2023
Westmead Hospital
2019-2020
MRC University of Glasgow Centre for Virus Research
2009
ABSTRACT Several human cytomegalovirus (HCMV) genes encode products that modulate cellular functions in a manner likely to enhance viral pathogenesis. This includes UL111A , which encodes homologs of interleukin-10 (hIL-10). Depending upon signals received, monocytes and macrophages become polarized either classically activated (M1 proinflammatory) or alternatively (M2 anti-inflammatory) subsets. Skewing polarization toward an M2 subset may benefit the virus by limiting proinflammatory...
The human cytomegalovirus (HCMV) gene UL111A encodes cytomegalovirus-encoded interleukin-10 (cmvIL-10), a homolog of the potent immunomodulatory cytokine interleukin 10 (hIL-10). This viral exhibits range functions, including suppression proinflammatory production and dendritic cell (DC) maturation, as well inhibition major histocompatibility complex (MHC) class I II. Here, we present data showing that cmvIL-10 upregulates hIL-10, identify CD14(+)monocytes monocyte-derived macrophages DCs...
Human cytomegalovirus (HCMV) causes a lifelong infection through establishment of latency. Although reactivation from latency can cause life-threatening disease, our molecular understanding HCMV is incomplete. Here we use single cell RNA-seq analysis to characterize in monocytes and hematopoietic stem progenitor cells (HSPCs). In monocytes, identify host surface markers that enable enrichment latent harboring higher viral transcript levels, which reactivate more efficiently, are...
Virus-specific T-cells (VSTs) from third-party donors mediate short- and long-term antiviral effects in allogeneic hematopoietic stem cell transplant (HSCT) recipients with relapsed or refractory viral infections. We investigated early administration of VSTs, together therapy patients requiring treatment for first cytomegalovirus (CMV) Epstein-Barr virus (EBV) infection. Thirty HSCT were treated 1 to 4 VST infusions (2 × 107 cells/m2; CMV n=27, EBV n=3) at a median days after initiation...
ABSTRACT The UL111A gene of human cytomegalovirus encodes a viral homologue the cellular immunomodulatory cytokine interleukin 10 (cIL-10), which, due to alternative splicing, results in expression two isoforms designated LAcmvIL-10 (expressed during both lytic and latent infection) cmvIL-10 (identified only infection). We have analyzed functions infection primary myeloid progenitor cells found that is responsible, at least part, for known increase secretion IL-10 CCL8 secretomes latently...
Cytomegalovirus (HCMV) contains cholesterol, but how HCMV interacts with host cholesterol metabolism is unknown. We found that, in human fibroblasts, infection increased the efflux of cellular despite reducing abundance ABCA1. Mechanistically, viral protein US28 was acting through CDC42, rearranging actin microfilaments, causing association lipid rafts, and leading to a dramatic change and/or structure rafts. These changes displaced ABCA1 from cell surface created new binding sites for...
Herpesviruses are known to encode a number of inhibitors host cell death, including RIP Homotypic Interaction Motif (RHIM)-containing proteins. Varicella zoster virus (VZV) is member the alphaherpesvirus subfamily and responsible for causing chickenpox shingles. We have identified novel viral RHIM in VZV capsid triplex protein, open reading frame (ORF) 20, that acts as death inhibitor. Like human cellular RHIMs RIPK1 RIPK3 stabilise necrosome TNF-induced necroptosis, M45 from murine...
Adoptive immunotherapy using donor-derived antigen-specific T-cells can prevent and treat infection after allogeneic haemopoietic stem cell transplant (HSCT).We treated 11 patients with a prophylactic infusion of 2 × 107 cells per square metre targeting seven infections (six viral one fungal) following HSCT. Targeted pathogens were cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, varicella zoster virus, influenza, BK (BKV) Aspergillus fumigatus.T-cell products successfully...
The human cytomegalovirus UL111A gene is expressed during latent and productive infections, it codes for homologs of interleukin-10 (IL-10). We examined whether viral IL-10 latency altered differentiation latently infected myeloid progenitors. In comparison to infection with parental virus or mock infection, a in which the encoding has been deleted upregulated cytokines associated dendritic cell (DC) formation increased proportion DCs. These data demonstrate that restricts ability...
Human cytomegalovirus (HCMV) is a ubiquitous human herpesvirus. While HCMV infection generally asymptomatic in the immunocompetent, it can have devastating consequences those with compromised or underdeveloped immune systems, including transplant recipients and neonates. Galectins are widely expressed protein family that been demonstrated to modulate both antiviral immunity regulate direct host-virus interactions. The potential for galectins directly has not previously studied, our results...
Abstract Objectives Cytomegalovirus (CMV) is known to have a significant impact on immune recovery post‐allogeneic haemopoietic stem cell transplant (HSCT). Adoptive therapy with donor‐derived or third‐party virus‐specific T cells (VST) can restore CMV immunity leading clinical benefit in prevention and treatment of post‐HSCT infection. We developed mass cytometry approach study natural assess the mechanisms underlying benefits observed recipients VST. Methods A panel 38 antibodies was...
Human cytomegalovirus (HCMV) is the most frequent cause of opportunistic viral infection following transplantation. Viral factors potential clinical importance include selection mutants resistant to antiviral drugs and occurrence infections involving multiple HCMV strains. These are typically addressed by analyzing relevant genes PCR Sanger sequencing, which involves independent assays limited sensitivity. To assess dynamics populations with high sensitivity, we applied high-throughput...
Abstract Human cytomegalovirus reactivation is a major opportunistic infection after allogeneic haematopoietic stem cell transplantation and has complex relationship with post-transplant immune reconstitution. Here, we use mass cytometry to define patterns of innate adaptive reconstitution at key phases human in the first 100 days post transplantation. associated development activated, memory T-cell profiles, faster effector-memory CD4 + recovery patients low-level versus high-level DNAemia....
Human cytomegalovirus (HCMV) is a herpesvirus with both lytic and latent life cycles. encodes 2 viral cytokines that are orthologs of human cellular interleukin 10 (cIL-10). Both (cmvIL-10) Latency-associated (LAcmvIL-10) (collectively vIL-10) expressed during infection cause immunosuppressive effects impede virus clearance. LAcmvIL-10 also myeloid progenitor cells monocytes facilitates persistence. Here, we investigated whether vIL-10 could be detected natural infection.Plasma from healthy...
The human cytomegalovirus (HCMV) ORF94 gene product has been reported to be expressed during both productive and latent phases of infection, although its function is unknown. We report that expression pORF94 leads decreased 2',5'-oligoadenylate synthetase (OAS) in transfected cells with without interferon stimulation. Furthermore, the functional activity OAS was inhibited by pORF94. Finally, we present evidence modulation HCMV infection fibroblasts. This study provides first identification a...
Regulation of the lectin galectin 9 (Gal-9) was investigated for first time during human cytomegalovirus (HCMV) infection. Gal-9 transcription significantly upregulated in transplant recipients with reactivated HCMV vivo. In vitro, potently by independently viral gene expression, interferon beta (IFN-β) identified as mediator this effect. This study defines an immunoregulatory protein increased infection and a novel mechanism to control through IFN-β induction.
The effect of abrogating the interferon (IFN) response on human cytomegalovirus (HCMV) replication was investigated using primary cells engineered to block either production or type I IFNs. In IFN-deficient cells, HCMV produced larger plaques and spread replicated more rapidly than in parental cells. These demonstrate vital role IFNs controlling provide useful tools investigate IFN HCMV.