ORCID Profile
0000-0002-6051-3268
Current Organisation
University of Queensland Institute for Molecular Bioscience
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Publisher: American Society for Microbiology
Date: 14-09-2022
DOI: 10.1128/JVI.00999-22
Abstract: Arthritogenic alphaviruses are transmitted via mosquito bites through the skin, potentially causing debilitating diseases. Our understanding of how viral infection starts in the skin and how virus systemically disseminates to cause disease remains limited.
Publisher: Wiley
Date: 23-03-2018
DOI: 10.1002/ART.40403
Abstract: In the past decade, arboviruses-arthropod-borne viruses-have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus, an arbovirus that belongs to the alphavirus genus, is a reemerging arthritogenic virus that has caused explosive outbreaks since 2006, notably on Réunion Island, and more recently in the Caribbean, South America, India, and Southeast Asia. The severity of arthritic disease caused by chikungunya virus has prompted public health authorities in affected countries to develop specific guidelines to tackle this pathogen. Chikungunya virus disease manifests first as an acute stage of severe joint inflammation and febrile illness, which later progresses to a chronic stage, during which patients may experience debilitating and persisting articular pain for extended periods. This review aims to provide a broad perspective on current knowledge of chikungunya virus pathogenesis by identifying key clinical and experimental studies that have contributed to our understanding of chikungunya virus to date. In addition, the review explores the practical aspects of treatment and management of both acute and chronic chikungunya virus based on clinical experience during chikungunya virus outbreaks. Finally, recent findings on potential therapeutic solutions-from antiviral agents to immunomodulators-are reviewed to provide both viral immunologists and clinical rheumatologists with a balanced perspective on the nature of a reemerging arboviral disease of significant public health concern, and insight into future therapeutic approaches to better address the treatment and management of chikungunya virus.
Publisher: American Society for Microbiology
Date: 28-04-2020
Abstract: Arthritogenic alphaviruses cause debilitating inflammatory disease, and current therapies are restricted to palliative approaches. Here, we show that following monocyte-driven muscle inflammation, tissue recovery is associated with the accumulation of CX 3 CR1 + macrophages in the muscle. Modulating inflammatory monocyte infiltration using immune-modifying microparticles (IMP) reduced tissue damage and inflammation and enhanced the formation of tissue repair-associated CX 3 CR1 + macrophages in the muscle. This shows that modulating key effectors of viral inflammation using microparticles can alter the outcome of disease by facilitating the accumulation of macrophage subsets associated with tissue repair.
Publisher: Public Library of Science (PLoS)
Date: 10-02-2022
DOI: 10.1371/JOURNAL.PPAT.1010185
Abstract: Arthritogenic alphaviruses are mosquito-borne viruses that are a major cause of infectious arthropathies worldwide, and recent outbreaks of chikungunya virus and Ross River virus (RRV) infections highlight the need for robust intervention strategies. Alphaviral arthritis can persist for months after the initial acute disease, and is mediated by cellular immune responses. A common strategy to limit inflammation and pathology is to d en the overwhelming inflammatory responses by modulating proinflammatory cytokine pathways. Here, we investigate the contribution of interleukin-17 (IL-17), a cytokine involved in arthropathies such as rheumatoid arthritis, in the development RRV-induced arthritis and myositis. IL-17 was quantified in serum from RRV-infected patients, and mice were infected with RRV and joints and muscle tissues collected to analyse cellular infiltrates, tissue mRNA, cytokine expression, and joint and muscle histopathology. IL-17 expression was increased in musculoskeletal tissues and serum of RRV-infected mice and humans, respectively. IL-17–producing T cells and neutrophils contributed to the cellular infiltrate in the joint and muscle tissue during acute RRV disease in mice. Blockade of IL-17A/F using a monoclonal antibody (mAb) reduced disease severity in RRV-infected mice and led to decreased proinflammatory proteins, cellular infiltration in synovial tissues and cartilage damage, without affecting viral titers in inflamed tissues. IL-17A/F blockade triggered a shift in transcriptional profile of both leukocyte infiltrates and musculoskeletal stromal cells by downregulating proinflammatory genes. This study highlights a previously uncharacterized role for an effector cytokine in alphaviral pathology and points towards potential therapeutic benefit in targeting IL-17 to treat patients presenting with RRV-induced arthropathy.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 25-04-2023
DOI: 10.1126/SCISIGNAL.ABQ1366
Abstract: Macrophages are key cellular contributors to the pathogenesis of COVID-19, the disease caused by the virus SARS-CoV-2. The SARS-CoV-2 entry receptor ACE2 is present only on a subset of macrophages at sites of SARS-CoV-2 infection in humans. Here, we investigated whether SARS-CoV-2 can enter macrophages, replicate, and release new viral progeny whether macrophages need to sense a replicating virus to drive cytokine release and, if so, whether ACE2 is involved in these mechanisms. We found that SARS-CoV-2 could enter, but did not replicate within, ACE2-deficient human primary macrophages and did not induce proinflammatory cytokine expression. By contrast, ACE2 overexpression in human THP-1–derived macrophages permitted SARS-CoV-2 entry, processing and replication, and virion release. ACE2-overexpressing THP-1 macrophages sensed active viral replication and triggered proinflammatory, antiviral programs mediated by the kinase TBK-1 that limited prolonged viral replication and release. These findings help elucidate the role of ACE2 and its absence in macrophage responses to SARS-CoV-2 infection.
Publisher: American Society for Microbiology
Date: 26-04-2022
Abstract: CHIKV has been prevalent in Africa, Asia, and the Indian Ocean Islands for decades. There are currently no clinically approved vaccines or specific antiviral drugs targeting CHIKV.
Publisher: Frontiers Media SA
Date: 05-03-2020
Publisher: American Society for Microbiology
Date: 28-06-2022
Abstract: SARS-CoV-2 variants, with the threat of increased transmissibility, infectivity, and immune escape, continue to emerge as the COVID-19 pandemic progresses. Detailing the pathogenesis of disease caused by SARS-CoV-2 variants, such as Delta, is essential to better understand the clinical threat caused by emerging variants and associated disease.
Publisher: MDPI AG
Date: 22-03-2019
DOI: 10.3390/V11030290
Abstract: Arthritogenic alphaviruses are a group of medically important arboviruses that cause inflammatory musculoskeletal disease in humans with debilitating symptoms, such as arthralgia, arthritis, and myalgia. The arthritogenic, or Old World, alphaviruses are capable of causing explosive outbreaks, with some viruses of major global concern. At present, there are no specific therapeutics or commercially available vaccines available to prevent alphaviral disease. Infected patients are typically treated with analgesics and non-steroidal anti-inflammatory drugs to provide often inadequate symptomatic relief. Studies to determine the mechanisms of arthritogenic alphaviral disease have highlighted the role of the host immune system in disease pathogenesis. This review discusses the current knowledge of the innate immune response to acute alphavirus infection and alphavirus-induced immunopathology. Therapeutic strategies to treat arthritogenic alphavirus disease by targeting the host immune response are also examined.
Location: Australia
No related grants have been discovered for Helen Mostafavi.