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Scott A. Read

Bio: Scott A. Read is an academic researcher from University of Sydney. The author has contributed to research in topics: Hepatitis C virus & Immune system. The author has an hindex of 14, co-authored 33 publications receiving 653 citations.

Papers
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Journal ArticleDOI
TL;DR: This review summarizes current basic science and clinical evidence examining zinc as a direct antiviral, as well as a stimulant of antiviral immunity as a preventative and therapeutic treatment for viral infections.

444 citations

Journal ArticleDOI
TL;DR: This review will explore the unique mechanisms by which different oncogenic viruses induce inflammation to promote cancer initiation and progression.

64 citations

Journal ArticleDOI
17 Jun 2019-Cells
TL;DR: Micronutrient deficiencies develop for a variety of reasons, whether geographic, socioeconomic, nutritional, or as a result of disease pathologies such as chronic viral infection, and their role in the pathogenesis of HCV infection and in the response to antiviral therapy is explored.
Abstract: Micronutrient deficiencies develop for a variety of reasons, whether geographic, socioeconomic, nutritional, or as a result of disease pathologies such as chronic viral infection. As micronutrients are essential for a strong immune response, deficiencies can significantly dampen both the innate and the adaptive arms of antiviral immunity. The innate immune response in particular is crucial to protect against hepatitis C virus (HCV), a hepatotropic virus that maintains chronic infection in up to 80% of individuals if left untreated. While many micronutrients are required for HCV replication, an overlapping group of micronutrients are also necessary to enact a potent immune response. As the liver is responsible for the storage and metabolism of many micronutrients, HCV persistence can influence the micronutrients’ steady state to benefit viral persistence both directly and by weakening the antiviral response. This review will focus on common micronutrients such as zinc, iron, copper, selenium, vitamin A, vitamin B12, vitamin D and vitamin E. We will explore their role in the pathogenesis of HCV infection and in the response to antiviral therapy. While chronic hepatitis C virus infection drives deficiencies in micronutrients such as zinc, selenium, vitamin A and B12, it also stimulates copper and iron excess; these micronutrients influence antioxidant, inflammatory and immune responses to HCV.

52 citations

Journal ArticleDOI
TL;DR: It is shown that the rs12979860 CC genotype correlates with increased hepatic metallothionein expression through increased systemic zinc levels, providing the first evidence that zinc can act as a potent and specific inhibitor of IFN-λ3 signalling and highlight its potential as a target of therapeutic intervention for IFN -λ3-mediated chronic disease.
Abstract: Lambda interferons (IFNL, IFN-λ) are pro-inflammatory cytokines important in acute and chronic viral infection. Single-nucleotide polymorphisms rs12979860 and rs8099917 within the IFNL gene locus predict hepatitis C virus (HCV) clearance, as well as inflammation and fibrosis progression in viral and non-viral liver disease. The underlying mechanism, however, is not defined. Here we show that the rs12979860 CC genotype correlates with increased hepatic metallothionein expression through increased systemic zinc levels. Zinc interferes with IFN-λ3 binding to IFNL receptor 1 (IFNLR1), resulting in decreased antiviral activity and increased viral replication (HCV, influenza) in vitro. HCV patients with high zinc levels have low hepatocyte antiviral and inflammatory gene expression and high viral loads, confirming the inhibitory role of zinc in vivo. We provide the first evidence that zinc can act as a potent and specific inhibitor of IFN-λ3 signalling and highlight its potential as a target of therapeutic intervention for IFN-λ3-mediated chronic disease.

45 citations

Journal ArticleDOI
TL;DR: It is demonstrated that macrophages are primary responders to IFN-λ, uniquely positioned to bridge the gap between IFn-λ producing cells and lymphocyte populations that are not intrinsically responsive to IFE, highlighting a novel role for macrophage in shaping IFN -λ dependent immune responses.
Abstract: Lambda interferons (IFN-λs) are a major component of the innate immune defense to viruses, bacteria, and fungi. In human liver, IFN-λ not only drives antiviral responses, but also promotes inflammation and fibrosis in viral and non-viral diseases. Here we demonstrate that macrophages are primary responders to IFN-λ, uniquely positioned to bridge the gap between IFN-λ producing cells and lymphocyte populations that are not intrinsically responsive to IFN-λ. While CD14+ monocytes do not express the IFN-λ receptor, IFNLR1, sensitivity is quickly gained upon differentiation to macrophages in vitro. IFN-λ stimulates macrophage cytotoxicity and phagocytosis as well as the secretion of pro-inflammatory cytokines and interferon stimulated genes that mediate immune cell chemotaxis and effector functions. In particular, IFN-λ induced CCR5 and CXCR3 chemokines, stimulating T and NK cell migration, as well as subsequent NK cell cytotoxicity. Using immunofluorescence and cell sorting techniques, we confirmed that human liver macrophages expressing CD14 and CD68 are highly responsive to IFN-λ ex vivo. Together, these data highlight a novel role for macrophages in shaping IFN-λ dependent immune responses both directly through pro-inflammatory activity and indirectly by recruiting and activating IFN-λ unresponsive lymphocytes.

40 citations


Cited by
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Journal ArticleDOI
24 Dec 2004-Science

1,949 citations

Journal ArticleDOI
TL;DR: This 11th edition of the book Modern Nutrition in Health and Disease, featuring the work of more than 190 expert authors and divided into five parts, fully explains and encapsulates the fundamentals of nutrition and its role in contemporary society.
Abstract: This 11th edition of the book Modern Nutrition in Health and Disease, featuring the work of more than 190 expert authors and divided into five parts, fully explains and encapsulates the fundamentals of nutrition and its role in contemporary society, from mastering the basic science of nutrient metabolism and function to applying nutritional concepts to combat human disease. Part I comprehensively covers specific dietary components, including major dietary constituents, minerals, vitamins and other Other CABI sites 

1,105 citations

Journal ArticleDOI
TL;DR: This is the first demonstration of RNAi following ingestion of dsRNA in all of the species tested, and the method offers promise of both higher throughput RNAi screens and the development of a new generation of species-specific insecticides.

542 citations

01 Jan 2010
Abstract: BACKGROUND & AIMS A cascade of precursor lesions (eg, atrophic gastritis, intestinal metaplasia, and dysplasia) precedes most gastric adenocarcinomas. Quantification of gastric cancer risk in patients with premalignant gastric lesions is unclear, however. Consequently, endoscopic surveillance is controversial, especially in Western populations. METHODS To analyze current surveillance practice and gastric cancer risk in patients with premalignant gastric lesions, all patients with a first diagnosis between 1991 and 2004 were identified in the Dutch nationwide histopathology registry (PALGA); follow-up data were evaluated until December 2005. RESULTS In total, 22,365 (24%) patients were diagnosed with atrophic gastritis, 61,707 (67%) with intestinal metaplasia, 7616 (8%) with mild-to-moderate dysplasia, and 562 (0.6%) with severe dysplasia. Patients with a diagnosis of atrophic gastritis, intestinal metaplasia, or mild-to-moderate dysplasia received re-evaluation in 26%, 28%, and 38% of cases, respectively, compared with 61% after a diagnosis of severe dysplasia (P < .001). The annual incidence of gastric cancer was 0.1% for patients with atrophic gastritis, 0.25% for intestinal metaplasia, 0.6% for mild-to-moderate dysplasia, and 6% for severe dysplasia within 5 years after diagnosis. Risk factors for gastric cancer development were increasing severity of premalignant gastric lesions at initial diagnosis (eg, severe dysplasia, hazard ratio 40.14, 95% confidence interval 32.2-50.1), increased age (eg, 75-84 years, hazard ratio 3.75, 95% confidence interval 2.8-5.1), and male gender (hazard ratio 1.50, 95% CI 1.3-1.7). CONCLUSIONS Patients with premalignant gastric lesions are at considerable risk of gastric cancer. As current surveillance of these patients is inconsistent with their cancer risk, development of guidelines is indicated.

495 citations

Journal Article

494 citations