Generation and transmission of interlineage recombinants in the SARS-CoV-2 pandemic.

We present evidence for multiple independent origins of recombinant SARS-CoV-2 viruses sampled from late 2020 and early 2021 in the United Kingdom. Their genomes carry single-nucleotide polymorphisms and deletions that are characteristic of the B.1.1.7 variant of concern but lack the full complement of lineage-defining mutations. Instead, the remainder of their genomes share contiguous genetic variation with non-B.1.1.7 viruses circulating in the same geographic area at the same time as the recombinants. In four instances, there was evidence for onward transmission of a recombinant-origin virus, including one transmission cluster of 45 sequenced cases over the course of 2 months. The inferred genomic locations of recombination breakpoints suggest that every community-transmitted recombinant virus inherited its spike region from a B.1.1.7 parental virus, consistent with a transmission advantage for B.1.1.7's set of mutations.

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.

Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.

Context-specific emergence and growth of the SARS-CoV-2 Delta variant.

The SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences of COVID-19 worldwide1,2. The emergence of the Delta variant in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 SARS-CoV-2 genomes from England together with 93,649 genomes from the rest of the world to reconstruct the emergence of Delta and quantify its introduction to and regional dissemination across England in the context of changing travel and social restrictions. Using analysis of human movement, contact tracing and virus genomic data, we find that the geographic focus of the expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced more than 1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers reduced onward transmission from importations; however, the transmission chains that later dominated the Delta wave in England were seeded before travel restrictions were introduced. Increasing inter-regional travel within England drove the nationwide dissemination of Delta, with some cities receiving more than 2,000 observable lineage introductions from elsewhere. Subsequently, increased levels of local population mixing-and not the number of importations-were associated with the faster relative spread of Delta. The invasion dynamics of Delta depended on spatial heterogeneity in contact patterns, and our findings will inform optimal spatial interventions to reduce the transmission of current and future variants of concern, such as Omicron (Pango lineage B.1.1.529).

Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England.

The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England1, was first identified in the UK in late summer to early autumn 20202. Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number.

SCORPIO: a utility for defining and classifying mutation constellations of virus genomes.

SUMMARY: Scorpio provides a set of command line utilities for classifying, haplotyping, and defining constellations of mutations for an aligned set of genome sequences. It was developed to enable exploration and classification of variants of concern within the SARS-CoV-2 pandemic, but can be applied more generally to other species. AVAILABILITY AND IMPLEMENTATION: Scorpio is an open-source project distributed under the GNU GPL version 3 license. Source code and binaries are available at https://github.com/cov-lineages/scorpio, and binaries are also available from Bioconda. SARS-CoV-2 specific definitions can be installed as a separate dependency from https://github.com/cov-lineages/constellations.

Barriers and enablers to promoting grandchildren's physical activity and reducing screen time: a qualitative study with Australian grandparents.

BACKGROUND: With an increasing number of grandparents providing care to their grandchildren, calls have been made for these caregivers to be considered important stakeholders in encouraging children's engagement in health-promoting behaviors, such as physical activity. Understanding the perspectives of grandparents who provide care is crucial to informing efforts that aim to increase children's physical activity, yet little is understood about their perceptions of specific barriers and enablers to promoting children's physical activity and reducing screen time. The present study sought to explore these perceptions. METHODS: Semi-structured focus groups and individual interviews were conducted with grandparents who reported providing care to a grandchild aged 3 to 14 years. A total of 20 grandparents were sampled (mean age = 67.8 years). Data were subjected to reflexive thematic analysis. RESULTS: Key reported barriers to physical activity included (i) the effort (physical and logistical) and financial cost associated with organizing physical activities, (ii) grandparents' age and mobility issues (e.g., due to injury or illness), (iii) caring for children of different ages (e.g., older children having different physical activity interests than younger children), and (iv) a local environment that is not conducive to physical activity (e.g., lack of appropriate facilities). Barriers to reducing screen time included (i) parents sending children to care with electronic devices and (ii) children's fear of missing out on social connection that occurs electronically. Strategies and enablers of physical activity included (i) integrating activity into caregiving routines (e.g., walking the dog), (ii) involving grandchildren in decision making (e.g., asking them in which physical activities they wish to engage), (iii) encouraging grandchildren to engage in activity with other children, and (iv) creating a physical and social environment that supports activity (e.g., owning play equipment). A common strategy for reducing screen time was the creation of a home environment that is not conducive to this activity (e.g., removing electronic devices from view). CONCLUSIONS: Findings suggest that grandparents may benefit from resources that assist them to identify activities that are inexpensive and require minimal effort to organize. Activities that account for grandparents' age and health status, as well as any environmental barriers, are likely to be well-received.

Parents on the Concept of Physical Literacy: What Do They Know, What Do They Do, and What Do They Want?

Physical literacy development in early childhood, viewed by many as the foundation for lifelong physical activity engagement, is significantly influenced by parents. Our aim was to explore parents' understanding of physical literacy and gain insight into their perspectives on physical literacy promotion. We recruited 18 parents of children between 5 and 8 years old in Australia. Using semistructured interviews and thematic analysis, we identified several key issues regarding parents' understanding and implementation of physical literacy. Parents expressed interest in improving their implementation of physical literacy practices and had (often unintentionally) provided support for physical literacy subcomponents in the past. However, they described difficulties prioritizing physical literacy above other parental demands and expressed conflicting perceptions regarding where the responsibility should lie for developing their child's physical literacy (e.g., at home or at school). To ensure that the physical literacy "message" reaches parents, we encourage physical literacy promoters to consider the target (e.g., responsibility, priorities, and awareness) of their promotional strategies. Further investigation into the influence of sociocultural and economic factors on parents' understanding and application of physical literacy is warranted.

gofasta: command-line utilities for genomic epidemiology research.

SUMMARY: gofasta comprises a set of command-line utilities for handling alignments of short assembled genomes in a genomic epidemiology context. It was developed for processing large numbers of closely related SARS-CoV-2 viral genomes and should be useful with other densely sampled pathogen genomic datasets. It provides functions to convert sam-format pairwise alignments between assembled genomes to fasta format; to annotate mutations in multiple sequence alignments, and to extract sets of sequences by genetic distance measures for use in outbreak investigations. AVAILABILITY AND IMPLEMENTATION: gofasta is an open-source project distributed under the MIT license. Binaries are available at https://github.com/virus-evolution/gofasta, from Bioconda, and through the Go programming language's package management system. Source code and further documentation, including walkthroughs for common use cases, are available on the GitHub repository.

'It's been a lifelong thing for me': parents' experiences of facilitating a healthy lifestyle for their children with severe obesity.

OBJECTIVE: For parents and guardians, assisting children/adolescents with severe obesity to lose weight is often a key objective but a complex and difficult challenge. Our aim in this study was to explore parents' (and guardians') perspectives on the challenges they have faced in assisting their children/adolescents with severe obesity to lead a healthy lifestyle. METHODS: Thirteen parents/guardians were interviewed from a pool of families who had been referred but did not engage between 2016 and 2018 (N = 103), with the Perth Children's Hospital Healthy Weight Service, a clinical obesity program for children/adolescents (parent age M = 43.2 years, children age M = 10.3 years). Using semi-structured interviews and thematic analysis, we identified 3 broad themes. RESULTS: Parental weight-related factors reflected parents' own lifelong obesity narrative and its effect on their own and their families' ability to live a healthy lifestyle. Perceived inevitability of obesity in their child reflected parents' feelings that the obesity weight status of their children/adolescent was a persistent and overwhelming problem that felt 'out of control'. Lastly, parents reported challenges getting medical help stemming from co-morbid medical diagnosis in their child/adolescent, and difficulties with medical professionals. CONCLUSION: This study demonstrates that parents face challenges in supporting healthy lifestyle for children/adolescents with severe obesity due to parents own internal weight biases and their negative experiences within the healthcare system when seeking help.

Support needs and experiences of young people living in families with mental illness.

INTRODUCTION: Children and adolescents living in families affected by mental illness are at elevated risk of developing mental health problems. A range of interventions have been designed to help these young people; however, the effectiveness of these programs is, in some cases, mixed. Our aim was to understand in detail the support needs and experiences of a group of Australian children and adolescents living in families with mental illness. METHODS: Our study is a qualitative in nature. In 2020-2021, we interviewed 25 Australian young people (Mage = 13.60, SD = 2.26, 20 females and 5 males) living with family members affected by mental illness to understand their (the young people's) experiences, and to identify the types of support that these young people considered important or effective. We conducted reflexive thematic analyses of interview data, underpinned by interpretivist assumptions. RESULTS: We identified seven themes within two higher-order categories reflecting our aims to understand (1) lived experiences within families affected by mental illness (i.e., increased responsibilities, missing out, and stigmatization), and (2) support experiences, needs, and preferences (i.e., respite, shared experiences with like-minded others, education, and flexibility). CONCLUSIONS: Our findings hold substantial practical value by informing services, interventions, and conversations that better support young people living in families affected by mental illness.

Impact of vascular screening interventions on perceived threat, efficacy beliefs and behavioural intentions: a systematic narrative review.

Health-related behaviours contribute to the global burden of cardiovascular disease (CVD). Cardiovascular imaging can be used to screen asymptomatic individuals for increased risk of CVD to enable earlier interventions to promote health-related behaviours to prevent or reduce CVD risk. Some theories of behaviour and behaviour change assume that engagement in a given behaviour is a function of individual threat appraisals, beliefs regarding the performance of behaviour, self-efficacy for performing the desired behaviour and/or dispositions to act (e.g. behavioural intentions). To date, little is known about the impact of cardiovascular imaging interventions on these constructs. This article summarises evidence related to perceived threat, efficacy beliefs, and behavioural intentions after CVD screening. We identified 10 studies (2 RCTs and 8 non-randomised studies, n = 2498) through a combination of screening citations from published systematic reviews and meta-analyses and searching electronic databases. Of these, 7 measured behavioural intentions and perceived susceptibility and 3 measured efficacy beliefs. Findings showed largely encouraging effects of screening interventions on bolstering self-efficacy beliefs and strengthening behavioural intentions. Imaging results that suggest the presence of coronary or carotid artery disease also increased perceived susceptibility to CVD. However, the review also identified some gaps in the literature, such as a lack of guiding theoretical frameworks and assessments of critical determinants of health-related behaviours. By carefully considering the key issues highlighted in this review, we can make significant strides towards reducing CVD risks and improving population health.

This systematic narrative review sought to comprehensively report evidence related to individual responses to cardiovascular screening interventions. Theoretically, the study builds upon theories based on the cognitive perspective (e.g. Health Belief Model, Protection Motivation Theory), which supports the examination of individual perceptions of negative health-related outcomes or health risk, beliefs regarding the performance of a behaviour or outcome expectancies (e.g. perceived benefits of behavioural performance), personal control or capacity to perform a behaviour and/or willingness to invest the effort to engage in behaviour after behavioural intervention delivery. These concepts are considered key predictors of health-related behaviours and have been examined in several public health interventions. Using a variety of search strategies, studies that reported outcomes of interest were identified. Some studies showed that cardiovascular screening interventions may help people form the desired intention to engage in health-related behaviours. We also observed (largely) encouraging effects of cardiovascular screening interventions on individual confidence to engage in health-related behaviours and understanding of personal health risks. However, we identified some limitations in the design, delivery and outcomes assessed in the studies included. For future research, key recommendations to inform the design and delivery of health behaviour interventions are provided.

The Right Advice, from the Right Person, in the Right Way: Non-Engaged Consumer Families' Preferences for Lifestyle Intervention Design Relating to Severe Obesity in Childhood.

Family-based lifestyle interventions for children/adolescents with severe levels of obesity are numerous, but evidence indicates programs fail to elicit short- or longer-term weight loss outcomes. Families with lived experience can provide valuable insight as we strive to improve outcomes from programs. Our aim was to explore elements that families desired in a program designed to treat severe levels of obesity in young people. We recruited a cross-sectional sample of 13 families (parents and young people) who had been referred but had not engaged with the state-wide Perth Children's Hospital, Healthy Weight Service (Perth, Australia), between 2016 and 2018. Utilizing semi-structured interviews and reflexive qualitative thematic analysis, we identified two broad themes, (1) bridging the gap between what to do and how to do it, and (2) peers doing it with you. The first theme reflected parents' and young people's feelings that programs ought to teach specialist-designed practical strategies utilizing non-generic information tailored to address the needs of the family, in a collaboratively supportive way, and encourage young people to learn for themselves. The second theme reflected the importance of social connection facilitated by peer support, and intervention programs should be offered in a group format to foster inclusion. Families indicated a willingness to engage in tertiary intervention programs but desired support from specialized health professionals/programs to be tailored to their needs, sensitive to their experiences and challenges and provide useful practical strategies that support the knowledge-to-action process.

Perceptions of a family-based lifestyle intervention for children with overweight and obesity: a qualitative study on sustainability, self-regulation, and program optimization.

BACKGROUND: Family-based lifestyle interventions (FBLIs) are an important method for treating childhood weight problems. Despite being recognized as an effective intervention method, the optimal structure of these interventions for children's overweight and obesity has yet to be determined. Our aim was to better understand participants' (a) implementation of behaviour strategies and long-term outcomes, (b) perceptions regarding the optimal structure of FBLIs, and (c) insights into psychological concepts that may explain the success of these programs. METHODS: Purposive sampling was used to recruit participants. We conducted focus groups as well as one-to-one interviews with parents (n = 53) and children (n = 50; aged 7-13, M = 9.4 yr, SD = 3.1) three months following their involvement in a 10-week, multi-component, FBLI involving education and activities relating to healthy nutrition, physical activity, and behavior modification. Using an interpretivist approach, a qualitative study design was employed to examine participant experiences. RESULTS: We identified three higher-order categories: (a) participants' program experiences and perceptions (b) lifestyle changes post-program, and (c) recommendations for optimizing family-based programs. Themes identified within these categories included (a) support and structure & content, (b) diet and physical activity, and (c) in-program recommendations and post-program recommendations. CONCLUSIONS: We identified several challenges that can impair lasting behavior change (e.g., physical activity participation) following involvement in a FBLI. On optimizing these programs, participants emphasized fun, interactive content, interpersonal support, appropriate educational content, and behavior change techniques. Concepts rooted in motivational theory could help address calls for greater theoretical and mechanistic insight in FBLIs. Findings may support research advancement and assist health professionals to more consistently realize the potential of these interventions.

Longitudinal associations between formal volunteering and well-being among retired older people: follow-up results from a randomized controlled trial.

Volunteering has been identified as a potential mechanism for improving the psychosocial health of older adults. Utilizing a randomized controlled trial approach, the present study assessed the extent to which commencing volunteering can improve psychosocial health outcomes for older people. Fully retired Australian adults aged 60+ years (N= 445) were assessed at baseline and allocated to either the intervention or control arms of the trial. Those in the intervention condition were asked to participate in at least 60 min of formal volunteering per week for 6 months. Per-protocol analyses were conducted comparing psychosocial outcomes for those who complied with the intervention condition (n= 73) to outcomes for those who complied with the control condition (n= 112). Those who complied with the intervention condition demonstrated significant improvements in life satisfaction, purpose in life, and personal growth scores over a 12-month period relative to those in the control condition who did no volunteering. Findings provide evidence of a causal relationship between commencing volunteering and improvements in psychosocial health among older adults and indicate that encouraging participation in this activity could constitute an effective healthy aging intervention.

Delays in the Identification and Assessment of in-Hospital Stroke Patients.

OBJECTIVES: In-hospital stroke is associated with poor outcomes. Reasons for delays, use of interventions, and presence of large vessel occlusion are not well characterized. MATERIALS AND METHODS: A retrospective single center cohort of 97 patients with in-hospital stroke was analyzed to identify factors associated with delays from last known normal to symptom identification and to stroke team alerting. Stroke interventions and presence of large vessel occlusion were also assessed. RESULTS: Strokes were predominantly on surgery services (70%), ischemic (82%), and severe (median NIHSS 16; interquartile range [IQR] 6-24). There were long delays from last known normal to symptom identification (median 5.1 hours, IQR 1.0-19.7 hours), symptom identification to stroke team alerting (median 2.1 hours, IQR 0.5-9.9 hours), and total time from last known normal to alerting (median 11.4 [IQR 2.7-34.2] hours). In univariable analysis, being on a surgical service, in an ICU, intubated, and higher NIHSS were associated with delays. In multivariable analysis only intubation was independently associated with time from last known normal to symptom identification (coefficient 20 hours, IQR 0.2 - 39.8, p=0.047). Interventions were given to 17/80 (21%) ischemic stroke patients; 3 (4%) received IV tPA and 14 (18%) underwent thrombectomy. Vascular imaging occurred in 57/80 (71%) ischemic stroke patients and 21/57 (37%) had large vessel occlusion. CONCLUSIONS: Hospitalized patients with stroke experience long delays from symptom identification to stroke team alerting. Intubation was strongly associated with delay to symptom identification. Although stroke severity was high and large vessel occlusion common, many patients did not receive acute interventions.

MAN v FAT Soccer: Feasibility Study and Preliminary Efficacy of a Sport-Based Weight-Loss Intervention for Overweight and Obese Men in Australia.

MAN v FAT Soccer is a sport-based weight-loss program for overweight and obese men that originated in the United Kingdom (i.e., as MAN v FAT Football) and appears to successfully engage men with weight loss. We sought to explore whether the program would work in an Australian context by (a) establishing a foundation for the implementation of the program on a larger scale and (b) determining how large-scale implementation is most feasible. We conducted a nonrandomized, single intervention group feasibility trial of MAN v FAT Soccer in Australia with 418 male participants with a body mass index greater than 27.50 kg/m2. Results indicate that the program is acceptable, with participants reporting positive perceptions of the various components of the program and a high proportion reporting intentions to recommend the program to others (95.9%). Furthermore, preliminary effectiveness results indicate positive changes in weight (4.6% reduction) and physical activity (88.5% increase) and improvements in psychological outcomes such as depression (17.6% decrease), stress (19.0% decrease), and body appreciation (19.1% increase). Our findings provide general support for the feasibility of MAN v FAT Soccer and the notion that leveraging competition and masculinity may help drive men's health behavior change.

Likeability and perceived effectiveness of messages designed to encourage physical activity participation among older adults.

ISSUE ADDRESSED: Older adults are significantly less likely than their younger counterparts to engage in physical activity. Comprehensive policies to support healthy ageing thus need to include components encouraging greater participation in physical activity in later life. This study tested potential messages for use in health communication campaigns aimed at increasing physical activity among older adults. METHODS: Twelve written messages designed to encourage older adults to increase their levels of physical activity were rated by Australians aged 60-92 years (n = 369; 54% female) on the variables of likeability and perceived effectiveness. RESULTS: Ratings for all the tested messages were high across both outcome variables. The message Move more, live longer scored most favourably, with large majorities of participants liking this message (87%) and considering it effective (81%). Messages featuring rhyming or alliteration were rated significantly higher on both outcomes than messages without these attributes (all Ps < .001). CONCLUSIONS: Results provide insights into the types of messages that are likely to be accepted by older adults. Statements that use the phonological patterns of rhyming or alliteration are likely to be especially well received. SO WHAT?: Increasing participation in physical activity among older adults is critical to promoting the sustainability of health care systems and enhancing quality of life. The specific messaging attributes identified in the present study as being effective could be used by public health practitioners to inform their approach to physical activity messaging to older adults and incorporated into future health communication campaigns to increase their potential effectiveness with this target group.

Longitudinal integrated clerkship evaluations in UK medical schools: a narrative literature review.

PURPOSE: Longitudinal Integrated Clerkships (LICs) are a recognised model of curriculum design used internationally as an alternative to traditional block rotations in medical schools that have been shown to offer a multitude of educational benefits. As a relatively new development in the United Kingdom (UK), it is not yet clear whether these benefits will translate into a UK healthcare context. This article provides an early review of evaluations of UK LIC programmes. METHODS: A narrative literature review of LIC programme evaluations in UK medical schools. RESULTS: UK students and faculty found value in the LIC programmes with reported benefits including continuity of relationships, increased responsibility and purpose for students, a patient-centred approach and development of professional skills. However, students and GP tutors expressed initial anxieties adapting to the newness of the programme design and preparedness for exams. CONCLUSIONS: UK LIC programmes appear to be offering benefits for UK medical students and faculty members including personal and professional development in line with international literature. However, the current data is limited with significant gaps that need addressing for the impacts to be fully realised.

Classical swine fever virus Npro antagonises IRF3 to prevent IFN-independent TLR3 and RIG-I-mediated apoptosis.

Classical swine fever virus (CSFV) is the causative agent of classical swine fever, a notifiable disease of economic importance that causes severe leukopenia, fever and haemorrhagic disease in domesticated pigs and wild boar across the globe. CSFV has been shown to antagonise the induction of type I IFN, partly through a function of its N-terminal protease (Npro) which binds IRF3 and targets it for proteasomal degradation. Additionally, Npro has been shown to antagonise apoptosis triggered by the dsRNA-homolog poly(I:C), however the exact mechanism by which this is achieved has not been fully elucidated. In this study we confirm the ability of Npro to inhibit dsRNA-mediated apoptosis and show that Npro is also able to antagonise Sendai virus-mediated apoptosis in PK-15 cells. Gene edited PK-15 cell lines were used to show the dsRNA-sensing pathogen recognition receptors (PRRs) TLR3 and RIG-I specifically respond to poly(I:C) and SeV respectively, subsequently triggering apoptosis through pathways that converge on IRF3 and culminate in the cleavage of caspase-3. Importantly, this IRF3-mediated apoptosis was found to be dependent on transcription-independent functions of IRF3 and also on Bax, a pro-apoptotic Bcl-2 family protein, through a direct interaction between the two proteins. Deletion of IRF3, stable expression of Npro and infection with wild-type CSFV were found to antagonise the mitochondrial localisation of Bax, a key hallmark of the intrinsic, mitochondrial pathway of apoptosis. Together, these findings show that Npro's putative interaction with IRF3 is involved not only in its antagonism of type I IFN, but also dsRNA-mediated mitochondrial apoptosis.Importance Responsible for severe haemorrhagic disease in domestic pigs and wild boar, classical swine fever is recognised by the World Organisation for Animal Health (OIE) and European Union as a notifiable disease of economic importance. Persistent infection, immunotolerance and early dissemination of the virus at local sites of infection have been linked to the antagonism of type I IFN induction by Npro This protein may further contribute to these phenomena by antagonising the induction of dsRNA-mediated apoptosis. Ultimately, apoptosis is an important innate mechanism by which cells counter viruses at local sites of infection, thus preventing wider spread and dissemination within the host, potentially also contributing to the onset of persistence. Elucidation of the mechanism by which Npro antagonises the apoptotic response will help inform the development of rationally-designed live-attenuated vaccines and antivirals for control of outbreaks in typically CSFV-free countries.