A5055720036- HIV Research and Treatment
- HIV-related health complications and treatments
- HIV/AIDS Research and Interventions
- Atherosclerosis and Cardiovascular Diseases
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- Adipokines, Inflammation, and Metabolic Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Long-Term Effects of COVID-19
- Diabetes, Cardiovascular Risks, and Lipoproteins
- COVID-19 Clinical Research Studies
- Antioxidant Activity and Oxidative Stress
- Virus-based gene therapy research
- Advanced Glycation End Products research
- Characterization and Applications of Magnetic Nanoparticles
- RNA Interference and Gene Delivery
- Immune responses and vaccinations
- Systemic Lupus Erythematosus Research
- Peripheral Neuropathies and Disorders
- Tryptophan and brain disorders
- Erythrocyte Function and Pathophysiology
- Biosensors and Analytical Detection
Peter Doherty Institute
2022-2024
The University of Melbourne
2022-2024
Burnet Institute
2015-2024
MIT University
2015-2024
RMIT University
2015-2024
John Wiley & Sons (United States)
2022
Rush University Medical Center
2015
Chronic inflammation in older individuals is thought to contribute inflammatory, age-related diseases. Human monocytes are comprised of three subsets (classical, intermediate and nonclassical subsets), despite being critical regulators inflammation, the effect age on functionality monocyte remains be fully defined. In a cross-sectional study involving 91 healthy male (aged 20-84 years, median 52.4) 55 female 20-82 48.3) individuals, we found was associated with an increased proportion (P =...
BackgroundGenetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. The introduction global vaccine programs has contributed to lower COVID-19 hospitalisation and mortality rates, particularly in developed countries. In late 2021, Omicron BA.1 emerged, with substantially altered genetic differences clinical effects from other concern. Shortly after dominating spread early 2022, was supplanted by the genetically...
To compare the impact of HIV infection and healthy ageing on monocyte phenotype function determine whether age-related changes induced by are reversed in antiretroviral treated individuals.A cross sectional study markers viremic virologically suppressed HIV-positive males aged 45 years or less age-matched elderly (≥65 years) HIV-uninfected individuals.Age-related to were measured whole blood assays ex vivo both CD14(++)CD16(-) (CD14(+)) CD14(variable)CD16(+) (CD16(+)) subsets. Plasma...
Background Aging is associated with immune dysfunction and the related development of conditions an inflammatory pathogenesis. Some these changes are also observed in HIV infection, but interaction between aging infection unknown. Whilst sex differences innate immunity recognized, little research into has been performed on women. Methods This cross-sectional study positive negative women used whole blood flow cytometric analysis to characterize monocyte CD8+ T cell subsets. Plasma markers...
Human immunodeficiency virus (HIV) persistence in blood and tissue reservoirs, including the brain, is a major barrier to HIV cure possible cause of comorbid disease. However, size replication competent nature central nervous system (CNS) reservoir unclear. Here, we used intact proviral DNA assay (IPDA) provide first quantitative assessment defective brain people with (PWH).Total, intact, proviruses were measured autopsy frontal lobe from viremic (n = 18) or virologically suppressed 12) PWH....
We previously demonstrated that NK cells from HIV-infected individuals have elevated expression of activation markers, spontaneously degranulate ex vivo, and decrease a signal-transducing protein for NK-activating receptors, FcRγ. Importantly, these changes were maintained in virologically suppressed (VS) receiving combination antiretroviral therapy (cART). In this study, we show loss FcRγ is caused by the expansion novel subset FcRγ(-)CD56(dim) with an altered receptor repertoire biological...
HIV persistence in the brain is a barrier to cure, and potentially contributes HIV-associated neurocognitive disorders. Whether transcription persists despite viral suppression with antiretroviral therapy (ART) subject same blocks seen other tissues blood, unclear. Here, we quantified level of transcripts frontal cortex tissue from virally suppressed or non-virally people (PWH). transcriptional profiling (and PBMCs where available) (n = 11) PWH 13) was performed using digital polymerase...
HIV-infected (HIV+) individuals have an increased risk of atherosclerosis and cardiovascular disease which is independent antiretroviral therapy traditional factors. Monocytes play a central role in the development atherosclerosis, HIV-related chronic inflammation monocyte activation may contribute to but mechanisms are unknown.Using in-vitro model atherosclerotic plaque formation, we measured transendothelial migration purified monocytes from age-matched HIV+ uninfected donors examined...
Here, we provide the first regional analysis of intact and defective HIV reservoirs within brain. Brain tissue from both viremic virally suppressed people with (PWH) harbored pol DNA in all regions tested, lower levels present basal ganglia cerebellum relative to frontal white matter. Intact proviruses were primarily found matter but also detected other brain PWH, demonstrating as a major reservoir intact, potentially replication competent that persists despite antiretroviral therapy. ANN...
Chronic inflammation and immune activation occur in both HIV infection normal aging are associated with inflammatory disease. However, the degree to which influences age-related innate changes, biomarkers best reflect them, remains unclear.We measured established 309 individuals including 88 virologically suppressed (VS) 52 viremic (viral load ≤ >50 copies per milliliter, respectively) HIV-positive individuals. Levels of soluble (ie, CXCL10, CD163, neopterin) cellular proportions CD16...
Nanomedicine holds great promise for vascular disease diagnosis and specific therapy, yet rapid sequestration by the mononuclear phagocytic system limits efficacy of particle-based agents. The use low-fouling polymers, such as poly(ethylene glycol), efficiently reduces this immune recognition, but these nondegradable polymers can accumulate in human body may cause adverse effects after prolonged use. Thus, new particle formulations combining stealth, low immunogenicity biocompatible features...
Quantification of intact proviruses is a critical measurement in HIV cure studies both vitro and vivo. The widely adopted 'intact proviral DNA assay' (IPDA), designed to discriminate quantify genetically based on detection two sequence-specific targets, was originally validated using Bio-Rad's droplet digital PCR technology (ddPCR). Despite its advantages, ddPCR limited multiplexing capability (two-channel) labor- time intensive. To overcome some these limitations, we utilized nanowell-based...
Eradication of HIV cannot be achieved with combination antiretroviral therapy (cART) because the persistence long-lived latently infected resting memory CD4+ T cells. We previously reported that latency could established in cells presence chemokine CCL19. To define how CCL19 facilitated establishment latent infection, role receptor signalling was explored. In cells, induced phosphorylation RAC-alpha serine/threonine-protein kinase (Akt), nuclear factor kappa B (NF-κB),...
HIV-associated neurocognitive disorders (HAND) affect ~40% of virally suppressed people with HIV (PWH), however, the precise viral dependent and independent changes to brain are unclear. Here we characterized CNS reservoir immune environment SIV-infected (SIV+) rhesus macaques during acute (n = 4), chronic 12) or ART-suppressed SIV infection 11). Multiplex immunofluorescence for markers (vRNA/vDNA) activation was performed on frontal cortex matched colon tissue. SIV+ animals contained...
Abstract Continued high-level spread of SARS-CoV-2 has enabled an accumulation changes within the Spike glycoprotein, leading to resistance neutralising antibodies and concomitant entry requirements that increased viral transmission fitness. Herein, we demonstrate a significant change in angiotensin-converting enzyme 2 (ACE2) transmembrane serine protease (TMPRSS2) dependent by primary isolates occurred upon arrival Omicron lineages. Mechanistically show this shift be function two distinct...
Innate immune dysfunction persists in HIV+ individuals despite effective combination antiretroviral therapy (cART). We recently demonstrated that an adaptive-like CD56dim NK cell population lacking the signal transducing protein FcRγ is expanded individuals. Here, we analyzed a cohort of men who have sex with (MSM, n = 20) at baseline and following 6, 12, 24 months cART compared them uninfected MSM (n 15) to investigate impact on dysfunction. Proportions cells expressing markers early...
The role of high-density lipoprotein (HDL) function in HIV-related atherosclerotic cardiovascular disease (CVD) is unclear. HDLs isolated from HIV [HIV(+)HDL] and HIV-uninfected individuals [HIV(-)HDL] were assessed for HDL ability to promote monocyte-derived foam cell formation (MDFCF; a key event CVD) ex vivo.
Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Atherosclerosis, CAD, initiated by the transmigration innate immune monocytes to inflammatory sites deposited lipid called fatty streaks, which are present in arterial walls medium large arteries. The key pathogenic feature lesions at this early stage atherosclerosis maturation migrate into arteries form foam cells or lipid-laden macrophages. Considerable evidence supports hypothesis that risk increased...
Low high-density lipoprotein cholesterol (HDL-C) levels are one of the most powerful independent negative predictors atherosclerotic cardiovascular disease (CVD). The structure and function HDL rather than HDL-C may more accurately predict atherosclerosis. Several protein lipid compositional changes that impair occur in inflammatory states such as is usually determined by cell based assays efflux assay but these have numerous drawbacks lack standardization. Cell-free give robust measures...