Investigating interactions between influenza A virus and respiratory syncytial virus during coinfection

Respiratory viruses are the cause of significant disease burden and coinfections with more than one virus constitute between 10-30% of viral respiratory infections. Interactions among respiratory viruses are recognised for their importance in influencing viral dynamics, however direct virus-virus interactions are poorly understood. Influenza A virus (IAV) and respiratory syncytial virus (RSV) are important respiratory pathogens that share epidemiological characteristics, including timing of seasonal peaks of infections, and biological characteristics, including cellular tropism within the respiratory tract. To characterise interactions between IAV and RSV during coinfection, we developed an in vitro model in A549 cells, a cell line derived from the human lung. Analysis of viral growth kinetics and viral dynamics by live cell imaging showed that, while IAV replication appears unaffected by coinfection with RSV, RSV replication is significantly decreased in coinfection. Imaging of coinfected cells stained for IAV and RSV nucleoproteins and glycoproteins show that they localise to the same regions of the plasma membrane, suggesting there may be opportunity for viral interactions during viral assembly. To further explore this hypothesis, virus particles budding from coinfected cells were examined using super-resolution confocal microscopy. Filamentous structures extended from coinfected cells, that incorporated glycoproteins from both viruses in distinct patches along the filament. The ultra-structure of these filaments, determined by cryo-electron tomography, revealed the formation of chimeric viral particles (CVPs) that contained genomes and structural features from both IAV and RSV. Additionally, coinfection by IAV and RSV generated pseudotyped RSV filaments that incorporate IAV glycoproteins. Functional assays using a sialidase showed that CVPs can facilitate entry of IAV into cells that were stripped of IAV entry receptors, demonstrating CVPs possess expanded receptor tropism. To determine the likelihood for CVP formation in the airway epithelium, we coinfected primary differentiated human bronchial epithelial cell (hBEC) cultures at air-liquid interface. We observed that IAV and RSV infect ciliated epithelial cells and identified foci of coinfection. IAV and RSV proteins both localised at the apical surface of coinfected cells, providing opportunity for interactions to occur during viral assembly. Additionally, IAV and RSV replication kinetics and cytopathic effect in hBEC cultures reflected trends observed in the in vitro cell model, suggesting that viral interactions may be conserved between simplified and representative airway models. Overall, this project characterises interactions between IAV and RSV during coinfection and we show that coinfection by IAV and RSV results in formation of a novel class of viral particles. By expanding viral tropism, formation of CVPs may alter viral dissemination within the respiratory tract, potentially impacting disease outcomes for a coinfected individual. Further, by defining a previously unknown source of viral interaction with implications on viral structure, we contribute more widely to the understanding of the properties of IAV and RSV, and their infection biology as a whole

The Ursinus Weekly, October 18, 1948

Sophs apparently foiled as freshmen prexy, Lee Trimble, is safely hidden • WAA introduces \u2752 to Ursinus sports • Dale White elected editor of Lantern as Wentzel resigns • Football, fun, light fantastic promise successful old timers\u27 day celebration • Forum to feature election discussion • Grads get degrees on Founders\u27 Day • Five men appointed to act with faculty committees • Dressner, Buchanan picked as council representatives • German club plans dinner; to make Philadelphia trip • Thespians greet applicants at first meeting of year • Former student to return in concert with soprano • Frosh show ends customs for men • NSA head requests college democracy • A happy thought for hapless frosh • Freshman reviews first two weeks • Frosh live again after customs end • Soph ruler reveals innermost thoughts • Junior looks back on freshman year • Frosh views hist.1 with heavy heart • Modern miss visits ancient Latin lands • Subs work all year but get no credit • Dickinson romps to 24-0 victory over bear; Gerry Miller features with 85 yard runback • Bears seek victory on old timers\u27 day • Coeds triumph 5-2 in season\u27s opener • Mules trip bruins in soccer opener • Church colleges hit by Lafayette prexy • Footlighters start ambitious season • Staiger writes article for organic chemistry journal • Pre-meds plan activities; members need high gradeshttps://digitalcommons.ursinus.edu/weekly/1598/thumbnail.jp

Human rhinovirus infection blocks SARS-CoV-2 replication within the respiratory epithelium: implications for COVID-19 epidemiology

Virus-virus interactions influence the epidemiology of respiratory infections. However, the impact of viruses causing upper respiratory infections on SARS-CoV-2 replication and transmission is currently unknown. Human rhinoviruses cause the common cold and are the most prevalent respiratory viruses of humans. Interactions between rhinoviruses and co-circulating respiratory viruses have been shown to shape virus epidemiology at the individual host and population level. Here, we examined the replication kinetics of SARS-CoV-2 in the human respiratory epithelium in the presence or absence of rhinovirus. We show that human rhinovirus triggers an interferon response that blocks SARS-CoV-2 replication. Mathematical simulations show that this virus-virus interaction is likely to have a population-wide effect as an increasing prevalence of rhinovirus will reduce the number of new COVID-19 cases

Helical ordering of envelope‐associated proteins and glycoproteins in respiratory syncytial virus

Human respiratory syncytial virus (RSV) causes severe respiratory illness in children and the elderly. Here, using cryogenic electron microscopy and tomography combined with computational image analysis and three-dimensional reconstruction, we show that there is extensive helical ordering of the envelope-associated proteins and glycoproteins of RSV filamentous virions. We calculated a 16 Å resolution sub-tomogram average of the matrix protein (M) layer that forms an endoskeleton below the viral envelope. These data define a helical lattice of M-dimers, showing how M is oriented relative to the viral envelope. Glycoproteins that stud the viral envelope were also found to be helically ordered, a property that was coordinated by the M-layer. Furthermore, envelope glycoproteins clustered in pairs, a feature that may have implications for the conformation of fusion (F) glycoprotein epitopes that are the principal target for vaccine and monoclonal antibody development. We also report the presence, in authentic virus infections, of N-RNA rings packaged within RSV virions. These data provide molecular insight into the organisation of the virion and the mechanism of its assembly

Severe acute respiratory syndrome coronavirus 2 serosurveillance in a patient population reveals differences in virus exposure and antibody-mediated immunity according to host demography and healthcare setting

Identifying drivers of SARS-CoV-2 exposure and quantifying population immunity is crucial to prepare for future epidemics. We performed a serial cross-sectional serosurvey throughout the first pandemic wave among patients from the largest health board in Scotland. Screening of 7480 patient sera showed a weekly seroprevalence ranging from 0.10% to 8.23% in primary and 0.21% to 17.44% in secondary care, respectively. Neutralisation assays showed that around half of individuals who tested positive by ELISA assay, developed highly neutralising antibodies, mainly among secondary care patients. We estimated the individual probability of SARS-CoV-2 exposure and quantified associated risk factors. We show that secondary care patients, males and 45-64-year-olds exhibit a higher probability of being seropositive. The identification of risk factors and the differences in virus neutralisation activity between patient populations provided insights into the patterns of virus exposure during the first pandemic wave and shed light on what to expect in future waves

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Influenza A and respiratory syncytial virus trigger a cellular response that blocks severe acute respiratory syndrome virus 2 infection in the respiratory tract

No abstract available