e-Delphi in the outdoors: Stakeholder contributions to the development of a wellbeing-focused outdoor adventure education intervention program.

ISSUE ADDRESSED: Outdoor adventure education (OAE) (programs involving outdoor activities such as rock climbing or white-water canoeing) that participants perceive as risky, conducted in a social support setting, can be utilised by practitioners to elicit changes in educational and psychosocial outcomes to support participant adolescent wellbeing. METHODS: This study garnered the opinions of an expert OAE panel on the content of future programs aiming to impact adolescent wellbeing. The panel consisted of local (Western Australia, n = 7), national (Australia, n = 4), and international (Canada, Germany, New Zealand, United Kingdom, United States, n = 7) experts. A two-round, mixed-methods Delphi approach was employed. Extensive formative work led to the development of a series of open-ended questions requiring qualitative responses for round one. Panellists were also asked to respond to 17 statements using Likert scales in the second round. RESULTS: After analysis, a consensus was reached for all statements, with five statements having high consensus and being considered important by panellists. CONCLUSIONS: The statement 'Equity for all participants requires flexible delivery and facilitation' had the highest level of agreement amongst panellists. Connections, authentic experiences, and equitable experiences developed as key themes. SO WHAT?: Future OAE interventions focused on wellbeing impact could use the findings of this research as a basis for program design.

Exercise-induced responses in matrix metalloproteinases and osteopontin are not moderated by exercise format in males with overweight or obesity.

PURPOSE: Matrix metalloproteinase-2 (MMP-2) and -3 (MMP-3), and osteopontin (OPN) are associated with adipose-tissue expansion and development of metabolic disease. The purpose of the current study was to assess the circulating concentration of these markers, along with adiponectin and glucose concentrations, in response to acute exercise in individuals with overweight or obesity. METHODS: Fourteen sedentary males with overweight or obesity (29.0 ± 3.1 kg/m2) completed two separate, 3-day trials in randomised and counterbalanced order. An oral glucose tolerance test (OGTT) was performed on each day of the trial. Day two of each trial consisted of a single 30 min workload-matched bout of either high-intensity interval exercise (HIIE; alternating 100% and 50% of peak pulmonary oxygen uptake, [Formula: see text]O2peak) or continuous moderate intensity (CME; 60% [Formula: see text]O2peak) cycling completed 1 h prior to the OGTT. Glucose and physical activity were continuously monitored, while MMP-2, MMP-3, OPN and adiponectin were measured pre-, 0 h post-, 1 h post- and 25 h post-exercise. RESULTS: Exercise transiently increased MMP-3 and decreased OPN (both p < 0.01), but not MMP-2 or adiponectin. There were no differences in the response of inflammatory markers to the different exercise formats. Exercise increased mean daily glucose concentration and area under the glucose curve during the OGTT on Day 2 and Day 3 (main effect of time; p < 0.05). CONCLUSION: Acute cycling exercise decreased OPN, which is consistent with longer term improvements in cardiometabolic health and increased MMP-3, which is consistent with its role in tissue remodelling. Interestingly, exercise performed prior to the morning OGTT augmented the glucose concentrations in males. TRIAL REGISTRATION: ACTRN12613001086752.

"I love being in the outdoors": A qualitative descriptive study of outdoor adventure education program components for adolescent wellbeing.

BACKGROUND: This qualitative descriptive study gauged the perceptions of adolescent focus group participants and outdoor adventure education teachers on their preferred program components to improve adolescent wellbeing during a secondary school outdoor adventure education program. METHODS: Five student focus groups (N = 29) and four key informant interviews were conducted. Manual clustering of transcripts and template thematic analysis involving the development of a priori codes from interview questions resulted in an initial deductive code frame, followed by an inductive coding process. FINDINGS: Six themes were developed, namely perceptions of the outdoors, motivators for participation, barriers to participation, staff traits, and ideal program components. The main findings were that self-efficacy, resilience, and individual empowerment opportunities were highly valued. Students also valued autonomy and independence, which presented a challenge for teachers managing the risks of their programs. Social connections and relationships were also held in high regard. CONTRIBUTION: Whilst adrenalin-fuelled adventurous activities such as white water canoeing or rock climbing were popular with students and staff, the most valued aspects of outdoor adventure education were the opportunities to develop relationships, build social connections, self-efficacy, resilience, and a sense of individual empowerment. Greater access to this style of education for adolescent students from lower socio-economic areas would be beneficial due to the extant "opportunity gap" for this population.

Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced pulmonary function, respiratory failure and death. Bleomycin (Blm)-induced lung fibrosis in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates of predominantly B-cells that accumulate in the lung adjacent to areas of active fibrosis. We have shown previously a requirement for B-cells in the development of Blm-induced lung fibrosis in mice. To determine the therapeutic potential of inhibiting B-cell function in pulmonary fibrosis, we examined the effects of anti-CD20 B-cell ablation therapy to selectively remove mature B-cells from the immune system and inhibit Blm-induced lung fibrosis. Anti-CD20 B-cell ablation did not reduce fibrosis in this model; however, immune phenotyping of peripheral blood and lung resident cells revealed that anti-CD20-treated mice retained a high frequency of CD19+ CD138+ plasma cells. Interestingly, high levels of CD138+ cells were also identified in the lung tissue of patients with IPF, consistent with the mouse model. Treatment of mice with bortezomib, which depletes plasma cells, reduced the level of Blm-induced lung fibrosis, implicating plasma cells as important effector cells in the development and progression of pulmonary fibrosis.

Acute T-Cell-Driven Inflammation Requires the Endoglycosidase Heparanase-1 from Multiple Cell Types.

It has been accepted for decades that T lymphocytes and metastasising tumour cells traverse basement membranes (BM) by deploying a battery of degradative enzymes, particularly proteases. However, since many redundant proteases can solubilise BM it has been difficult to prove that proteases aid cell migration, particularly in vivo. Recent studies also suggest that other mechanisms allow BM passage of cells. To resolve this issue we exploited heparanase-1 (HPSE-1), the only endoglycosidase in mammals that digests heparan sulfate (HS), a major constituent of BM. Initially we examined the effect of HPSE-1 deficiency on a well-characterised adoptive transfer model of T-cell-mediated inflammation. We found that total elimination of HPSE-1 from this system resulted in a drastic reduction in tissue injury and loss of target HS. Subsequent studies showed that the source of HPSE-1 in the transferred T cells was predominantly activated CD4+ T cells. Based on bone marrow chimeras, two cellular sources of HPSE-1 were identified in T cell recipients, one being haematopoiesis dependent and the other radiation resistant. Collectively our findings unequivocally demonstrate that an acute T-cell-initiated inflammatory response is HPSE-1 dependent and is reliant on HPSE-1 from at least three different cell types.

Loss of hnRNPLL-dependent splicing of Ptprc has no impact on B-cell development, activation and terminal differentiation into antibody-secreting cells.

The RNA-binding protein heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) controls alternative splicing of protein tyrosine phosphatase receptor type C (Ptprc) which encodes CD45. hnRNPLL deficiency leads to a failure in silencing Ptprc exons 4-6 causing aberrant expression of the corresponding CD45 isoforms, namely, CD45RA, RB and RC. While an N-ethyl-N-nitrosourea-induced point mutation in murine Hnrnpll results in loss of peripheral naïve T cells, its role in B-cell biology remains unclear. Here, we demonstrate that B-cell development in the bone marrow of Hnrnpllthu/thu mice is normal and the number of mature B-cell subsets in the spleen and peritoneal cavity is comparable to control littermates. In response to in vivo immunization, Hnrnpllthu/thu mice were deficient in generating germinal center (GC) B cells, and analysis of mixed bone marrow chimeras revealed that the GC B-cell deficiency was a B-cell extrinsic effect of the hnRNPLL mutation. Mature Hnrnpllthu/thu B cells proliferated normally in response to various B-cell receptor- and Toll-like receptor-mediated stimuli. Similarly, in vitro stimulation of mutant B cells led to normal generation of plasmablasts, but mutant plasmablasts failed to downregulate B220 expression because of the inability of cells to undergo proper CD45 pre-messenger RNA alternative splicing. These findings collectively suggest that, like in T and natural killer T cells, the mutation disrupts hnRNPLL-mediated alternative splicing of the Ptprc gene in plasmablasts, but this dysregulation of Ptprc alternative splicing does not affect the development and function of B cells.

Strength Training in Long-Distance Triathletes: Barriers and Characteristics.

ABSTRACT: Luckin, KM, Badenhorst, CE, Cripps, AJ, Landers, GJ, Merrells, RJ, Bulsara, MK, and Hoyne, GF. Strength training in long-distance triathletes: Barriers and characteristics. J Strength Cond Res 35(2): 495-502, 2021-The purpose of this investigation was to identify perceived and physical barriers toward the completion of concurrent strength training and endurance training in long-distance triathletes. Three hundred ninety long-distance triathletes (224 women, 166 men; age [y]: 39 ± 10) completed a 68-question self-administered, semiquantitative survey that assessed endurance and strength training characteristics, experience in triathlon, and perceived barriers regarding the completion of strength training. Mean training hours per week was 14.92 ± 5.25, with 54.6% reporting participation in strength training. Heavy strength training was the most commonly reported (39.4%), with significantly more men completing this form of strength training (p < 0.001). Results from subjects who did not complete strength training indicated that perceived time constraints (53.1%) in addition to lack of knowledge on exercise progression and form (52.5%) are prominent perceived barriers to strength training completion. Identification of the barriers perceived by long-distance triathletes that prevent them from completing concurrent strength training and endurance training may be useful for coaches, athletes, and sports scientists who seek to incorporate strength training for injury prevention and performance improvement.

Small-sided games can discriminate perceptual-cognitive-motor capability and predict disposal efficiency in match performance of skilled Australian footballers.

This study determined if small-sided games could discriminate perceptual-cognitive-motor skill in Australian Rules Footballers. Higher skilled Western Australian Football League (WAFL) (n = 17) and lesser skilled Amateur (n = 23) players were recruited. Participants played three small-sided games of three minutes. Each disposal was scored for decision-making and motor skill execution, with these scores combined for a total score. Mann-Whitney U tests indicated significantly superior mean decision-making by higher skilled (Median = 2.90, Range = 0.30) over lesser skilled (Median = 2.80, Range = 0.73) (p = .012) players. Execution score was not significantly different between groups. Linear mixed model analysis found higher skilled players (M = 5.32, SD = 1.19) scored significantly higher than lower skilled players (M = 4.90, SD = 1.52) on total score (p = .009). Large effect sizes were found for decision-making and total score relative to games and position played in WAFL players. High agreement of scoring was observed for an elite (inter-rater) and a novice (intra-rater) coaches. Linear mixed model analysis indicated mean total scores of WAFL players significantly predicted disposal efficiency in match performance (p = .011). Small-sided games can be easily implemented to identify talented players and assess perceptual-cognitive-motor skill.

Idiopathic pulmonary fibrosis and a role for autoimmunity.

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It is typically associated with extensive and progressive fibrosis, and is fatal and has limited treatment options. Characteristically IPF patients display large lymphocyte aggregates composed of CD3+ T cells and CD20+ B cells within the lung tissue that are located near sites of active fibrosis. In addition, IPF patients can have autoantibodies to a range of host antigens, suggesting a breakdown in immunological tolerance. In this review, we examine the role of T and B cells in IPF pathogenesis and discuss how loss of self-tolerance to lung-specific proteins could exacerbate disease progression in IPF. We discuss what these results mean in terms of future prospects for immunotherapy of IPF.

Memory T cell RNA rearrangement programmed by heterogeneous nuclear ribonucleoprotein hnRNPLL.

Differentiation of memory cells involves DNA-sequence changes in B lymphocytes but is less clearly defined in T cells. RNA rearrangement is identified here as a key event in memory T cell differentiation by analysis of a mouse mutation that altered the proportions of naive and memory T cells and crippled the process of Ptprc exon silencing needed to generate CD45RO in memory T cells. A single substitution in a memory-induced RNA-binding protein, hnRNPLL, destabilized an RNA-recognition domain that bound with micromolar affinity to RNA containing the Ptprc exon-silencing sequence. Hnrpll mutation selectively diminished T cell accumulation in peripheral lymphoid tissues but not proliferation. Exon-array analysis of Hnrpll mutant naive and memory T cells revealed an extensive program of alternative mRNA splicing in memory T cells, coordinated by hnRNPLL. A remarkable overlap with alternative splicing in neural tissues may reflect a co-opted strategy for diversifying memory T cells.

Genetic and cellular studies highlight that A Disintegrin and Metalloproteinase 19 is a protective biomarker in human prostate cancer.

BACKGROUND: Prostate cancer is the second most frequently diagnosed cancer in men worldwide. Current treatments include surgery, androgen ablation and radiation. Introduction of more targeted therapies in prostate cancer, based on a detailed knowledge of the signalling pathways, aims to reduce side effects, leading to better clinical outcomes for the patient. ADAM19 (A Disintegrin And Metalloproteinase 19) is a transmembrane and soluble protein which can regulate cell phenotype through cell adhesion and proteolysis. ADAM19 has been positively associated with numerous diseases, but has not been shown to be a tumor suppressor in the pathogenesis of any human cancers. Our group sought to investigate the role of ADAM19 in human prostate cancer. METHODS: ADAM19 mRNA and protein levels were assessed in well characterised human prostate cancer cohorts. ADAM19 expression was assessed in normal prostate epithelial cells (RWPE-1) and prostate cancer cells (LNCaP, PC3) using western blotting and immunocytochemistry. Proliferation assays were conducted in LNCaP cells in which ADAM19 was over-expressed. In vitro scratch assays were performed in PC3 cells over-expressing ADAM19. RESULTS: Immunohistochemical studies highlighted that ADAM19 protein levels were elevated in normal prostate tissue compared to prostate cancer biopsies. Results from the clinical cohorts demonstrated that high levels of ADAM19 in microarrays are positively associated with lower stage (p = 0.02591) and reduced relapse (p = 0.00277) of human prostate cancer. In vitro, ADAM19 expression was higher in RWPE-1 cells compared to LNCaP cells. In addition, human ADAM19 over-expression reduced LNCaP cell proliferation and PC3 cell migration. CONCLUSIONS: Taken together, our immunohistochemical and microarray results and cellular studies have shown for the first time that ADAM19 is a protective factor for human prostate cancer. Further, this study suggests that upregulation of ADAM19 expression could be of therapeutic potential in human prostate cancer.

The Role of Alternative Splicing in the Control of Immune Homeostasis and Cellular Differentiation.

Alternative splicing of pre-mRNA helps to enhance the genetic diversity within mammalian cells by increasing the number of protein isoforms that can be generated from one gene product. This provides a great deal of flexibility to the host cell to alter protein function, but when dysregulation in splicing occurs this can have important impact on health and disease. Alternative splicing is widely used in the mammalian immune system to control the development and function of antigen specific lymphocytes. In this review we will examine the splicing of pre-mRNAs yielding key proteins in the immune system that regulate apoptosis, lymphocyte differentiation, activation and homeostasis, and discuss how defects in splicing can contribute to diseases. We will describe how disruption to trans-acting factors, such as heterogeneous nuclear ribonucleoproteins (hnRNPs), can impact on cell survival and differentiation in the immune system.

Visualizing the role of Cbl-b in control of islet-reactive CD4 T cells and susceptibility to type 1 diabetes.

The E3 ubiquitin ligase Cbl-b regulates T cell activation thresholds and has been associated with protecting against type 1 diabetes, but its in vivo role in the process of self-tolerance has not been examined at the level of potentially autoaggressive CD4(+) T cells. In this study, we visualize the consequences of Cbl-b deficiency on self-tolerance to lysozyme Ag expressed in transgenic mice under control of the insulin promoter (insHEL). By tracing the fate of pancreatic islet-reactive CD4(+) T cells in prediabetic 3A9-TCR × insHEL double-transgenic mice, we find that Cbl-b deficiency contrasts with AIRE or IL-2 deficiency, because it does not affect thymic negative selection of islet-reactive CD4(+) cells or the numbers of islet-specific CD4(+) or CD4(+)Foxp3(+) T cells in the periphery, although it decreased differentiation of inducible regulatory T cells from TGF-ß-treated 3A9-TCR cells in vitro. When removed from regulatory T cells and placed in culture, Cblb-deficient islet-reactive CD4(+) cells reveal a capacity to proliferate to HEL Ag that is repressed in wild-type cells. This latent failure of T cell anergy is, nevertheless, controlled in vivo in prediabetic mice so that islet-reactive CD4(+) cells in the spleen and the pancreatic lymph node of Cblb-deficient mice show no evidence of increased activation or proliferation in situ. Cblb deficiency subsequently precipitated diabetes in most TCR:insHEL animals by 15 wk of age. These results reveal a role for peripheral T cell anergy in organ-specific self-tolerance and illuminate the interplay between Cblb-dependent anergy and other mechanisms for preventing organ-specific autoimmunity.

Immunological Phenotyping of Mice with a Point Mutation in Cdk4.

Cyclin-dependent kinases (CDKs) play a crucial role in regulation of the mammalian cell cycle. CDK4 and CDK6 control the G1/S restriction checkpoint through their ability to associate with cyclin D proteins in response to growth factor signals. CDK4 deficiency in mice gives rise to a range of endocrine-specific phenotypes including diabetes, infertility, dwarfism, and atrophy of the anterior pituitary. Although CDK6 deficiency can cause thymic atrophy due to a block in the double-negative (DN) to double-positive (DP) stage of T cell development, there are no overt defects in immune cell development reported for CDK4-deficient mice. Here, we examined the impact of a novel N-ethyl-N-nitrosourea-induced point mutation in the gene encoding CDK4 on immune cell development. Mutant mice (Cdk4wnch/wnch) showed normal development and differentiation of major immune cell subsets in the thymus and spleen. Moreover, T cells from Cdk4wnch/wnch mice exhibited normal cytokine production in response to in vitro stimulation. However, analysis of the mixed bone marrow chimeras revealed that Cdk4wnch/wnch-derived T cell subsets and NK cells are at a competitive disadvantage compared to Cdk4+/+-derived cells in the thymus and periphery of recipients. These results suggest a possible role for the CDK4wnch mutation in the development of some immune cells, which only becomes apparent when the Cdk4wnch/wnch mutant cells are in direct competition with wild-type immune cells in the mixed bone marrow chimera.

Emerging role of immune cells as drivers of pulmonary fibrosis.

The pathogenesis of pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and other forms of interstitial lung disease, involves a complex interplay of various factors including host genetics, environmental pollutants, infection, aberrant repair and dysregulated immune responses. Highly variable clinical outcomes of some ILDs, in particular IPF, have made it difficult to identify the precise mechanisms involved in disease pathogenesis and thus the development of a specific cure or treatment to halt and reverse the decline in patient health. With the advent of in-depth molecular diagnostics, it is becoming evident that the pathogenesis of IPF is unlikely to be the same for all patients and therefore will likely require different treatment approaches. Chronic inflammation is a cardinal feature of IPF and is driven by both innate and adaptive immune responses. Inflammatory cells and activated fibroblasts secrete various pro-inflammatory cytokines and chemokines that perpetuate the inflammatory response and contribute to the recruitment and activation of more immune cells and fibroblasts. The balance between pro-inflammatory and regulatory immune cell subsets, as well as the interactions between immune cell types and resident cells within the lung microenvironment, ultimately determines the extent of fibrosis and the potential for resolution. This review examines the role of the innate and adaptive immune responses in pulmonary fibrosis, with an emphasis on IPF. The role of different immune cell types is discussed as well as novel anti-inflammatory and immunotherapy approaches currently in clinical trial or in preclinical development.

Attributes of Expert Anticipation Should Inform the Design of Virtual Reality Simulators to Accelerate Learning and Transfer of Skill.

Expert sport performers cope with a multitude of visual information to achieve precise skill goals under time stress and pressure. For example, a major league baseball or cricket batter must read opponent variations in actions and ball flight paths to strike the ball in less than a second. Crowded playing schedules and training load restrictions to minimise injury have limited opportunity for field-based practice in sports. As a result, many sports organisations are exploring the use of virtual reality (VR) simulators. Whilst VR synthetic experiences can allow greater control of visual stimuli, immersion to create presence in an environment, and interaction with stimuli, compared to traditional video simulation, the underpinning mechanisms of how experts use visual information for anticipation have not been properly incorporated into its content design. In themes, this opinion article briefly explains the mechanisms underpinning expert visual anticipation, as well as its learning and transfer, with a view that this knowledge can better inform VR simulator content design. In each theme, examples are discussed for improved content design of VR simulators taking into consideration its advantages and limitations relative to video simulation techniques. Whilst sport is used as the exemplar, the points discussed have implications for skill learning in other domains, such as military and law enforcement. It is hoped that our paper will stimulate improved content design of VR simulators for future research and skill enhancement across several domains.

Consequences of increased CD45RA and RC isoforms for TCR signaling and peripheral T cell deficiency resulting from heterogeneous nuclear ribonucleoprotein L-like mutation.

CD45 is the most abundant protein tyrosine phosphatase in the plasma membrane of T cells and serves a critical role in TCR signaling. Different CD45 isoforms are made by alternative mRNA splicing depending on the stage of T cell development and activation, yet their role remains unclear. Expression of CD45RA and RC isoforms is increased 20- to 200-fold on T cells from thunder mice with a loss-of-function mutation in the RNA-binding protein, heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL), although total CD45 expression is unaltered. In this study, we test the hypothesis that this shift in CD45 isoform expression alters TCR signaling, thymic selection, and accumulation of peripheral T cells. There was no discernable effect of the change in CD45 isoform expression upon Lck phosphorylation or T cell positive and negative selection, whereas these indices were strongly affected by a decrease in the overall amount of CD45 in Ptprc mutant animals. The one exception to this conclusion was in thymocytes from Ptprc(loc/loc) animals with 4% of normal CD45 protein levels, where Lck505 phosphorylation was increased 25% in Hnrpll mutant cells, suggesting that high m.w. CD45 isoforms had lower Lck505 phosphatase activity in this context. In T cells with no CD45 protein, hnRNPLL mutation still diminished peripheral T cell accumulation, demonstrating that hnRNPLL regulates T cell longevity independently from its effects on CD45 splicing.

A cell autonomous role for the Notch ligand Delta-like 3 in αß T-cell development.

Notch signalling is critical to help direct T-cell lineage commitment in early T-cell progenitors and in the development of αß T-cells. Epithelial and stromal cell populations in the thymus express the Notch DSL (Delta, Serrate and Lag2)ligands Delta-like 1 (Dll1), Delta-like 4 (Dll4), Jagged 1 and Jagged 2, and induce Notch signalling in thymocytes that express the Notch receptor. At present there is nothing known about the role of the Delta-like 3 (Dll3) ligand in the immune system. Here we describe a novel cell autonomous role for Dll3 in αß T-cell development. We show that Dll3 cannot activate Notch when expressed in trans but like other Notch ligands it can inhibit Notch signalling when expressed in cis with the receptor. The loss of Dll3 leads to an increase in Hes5 expression in double positive thymocytes and their increased production of mature CD4(+) and CD8(+) T cells. Studies using competitive irradiation chimeras proved that Dll3 acts in a cell autonomous manner to regulate positive selection but not negative selection of autoreactive T cells. Our results indicate that Dll3 has a unique function during T-cell development that is distinct from the role played by the other DSL ligands of Notch and is in keeping with other recent studies indicating that Dll1 and Dll3 ligands have non-overlapping roles during embryonic development.

Mechanisms that regulate peripheral immune responses to control organ-specific autoimmunity.

The immune system must balance the need to maintain a diverse repertoire of lymphocytes to be able to fight infection with the need to maintain tolerance to self-proteins. The immune system places strict regulation over the ability of T cells to produce the major T cell growth factor interleukin 2 as this cytokine can influence a variety of immune outcomes. T cells require the delivery of two signals, one through the antigen receptor and a second through the costimulatory receptor CD28. The immune system uses a variety of E3 ubiquitin ligases to target signaling proteins that function downstream of the TCR and CD28 receptors. Mutations in these E3 ligases can lead to a breakdown in immune tolerance and development of autoimmunity. This paper will examine the role of a range of E3 ubiquitin ligases and signaling pathways that influence the development of T-cell effector responses and the development of organ-specific autoimmune diseases such as type 1 diabetes.

An Outbreak of Highly Pathogenic Avian Influenza (H7N7) in Australia and the Potential for Novel Influenza A Viruses to Emerge.

In 2020, several geographically isolated farms in Victoria, Australia, experienced an outbreak of highly pathogenic avian influenza (HPAI) virus H7N7 and low pathogenic avian influenza (LPAI) viruses H5N2 and H7N6. Effective containment and control measures ensured the eradication of these viruses but the event culminated in substantial loss of livestock and significant economic impact. The avian HPAI H7N7 virus generally does not infect humans; however, evidence shows the ocular pathway presents a favourable tissue tropism for human infection. Through antigenic drift, mutations in the H7N7 viral genome may increase virulence and pathogenicity in humans. The Victorian outbreak also detected LPAI H7N6 in emus at a commercial farm. Novel influenza A viruses can emerge by mixing different viral strains in a host susceptible to avian and human influenza strains. Studies show that emus are susceptible to infections from a wide range of influenza viral subtypes, including H5N1 and the pandemic H1N1. The emu's internal organs and tissues express abundant cell surface sialic acid receptors that favour the attachment of avian and human influenza viruses, increasing the potential for internal genetic reassortment and the emergence of novel influenza A viruses. This review summarises the historical context of H7N7 in Australia, considers the potential for increased virulence and pathogenesis through mutations and draws attention to the emu as potentially an unrecognised viral mixing vessel.