Coinfection by influenza A virus and respiratory syncytial virus produces hybrid virus particles

Haney, Joanne; Víjayakríshnan, Swetha; Streetley, James; Dee, Kieran; Goldfarb, Daniel; Clarke, Mairi; Mullin, Margaret; Carter, Stephen D.; Bhella, David; Murcia, Pablo R

doi:10.1038/s41564-022-01242-5

Cited by 45 publications

(38 citation statements)

References 50 publications

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“…Simultaneous detection of multiple viruses is frequent in both healthy children 8 and children with respiratory infections [8][9][10][11][12][13][14] , and virus-virus interactions can be either synergistic or antagonistic. A recent study showed that co-infection with influenza A virus and RSV can form hybrid viral particles in vitro, which evade neutralising antibodies and broaden receptor tropism 15 . In contrast, human rhinovirus (HRV) has been shown to interfere with influenza virus, reducing the chance of co-detection and cocirculation of both viruses at the individual and population levels, respectively 16 .…”

Section: Introductionmentioning

confidence: 99%

Association between disease severity and co-detection of respiratory pathogens in infants with RSV infection

Lin

Drysdale

Snape

et al. 2023

Preprint

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BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of hospitalisation associated with acute respiratory infection in infants and young children, with substantial disease burden globally. The impact of additional respiratory pathogens on RSV disease severity is not completely understood. OBJECTIVES: The objective of this study was to explore the associations between RSV disease severity and the presence of other respiratory pathogens. METHODS: Nasopharyngeal swabs were prospectively collected from two infant cohorts: a prospective longitudinal birth cohort study and an infant cross-sectional study recruiting infants <1 year of age with RSV infection in Spain, the UK, and the Netherlands during 2017-20 [part of the REspiratory Syncytial virus Consortium in EUrope (RESCEU) project]. The samples were sequenced using targeted metagenomic sequencing with a probe set optimised for high-resolution capture of sequences of over 100 pathogens, including all common respiratory viruses and bacteria. Viral genomes and bacterial genetic sequences were reconstructed. Associations between clinical severity and presence of other pathogens were evaluated after adjusting for potential confounders, including age, gestational age, RSV viral load, and presence of comorbidities. RESULTS: RSV was detected in 433 infants. Nearly one in four of the infants (24%) harboured at least one additional non-RSV respiratory virus, with human rhinovirus being the most frequently detected (15% of the infants), followed by seasonal coronaviruses (4%). In this cohort, RSV-infected infants harbouring any other virus tended to be older (median age: 4.3 vs. 3.7 months) and were more likely to require intensive care and mechanical ventilation than those who did not.Moraxella,Streptococcus, andHaemophilusspecies were the most frequently identified target bacteria, together found in 392 (91%) of the 433 infants (S. pneumoniaein 51% of the infants andH. influenzaein 38%). The strongest contributors to severity of presentation were younger age and the co-detection ofHaemophilusspecies alongside RSV. Across all age groups in both cohorts, detection ofHaemophilusspecies was associated with higher overall severity, as captured by ReSVinet scores, and specifically with increased rates of hospitalisation and respiratory distress. In contrast, presence ofMoraxellaspecies was associated with lower ReSVinet scores and reduced need for intensive care and mechanical ventilation. Infants with and withoutStreptococcusspecies (orS. pneumoniaein particular) had similar clinical outcomes. No specific RSV strain was associated with co-detection of other pathogens. CONCLUSION: Our findings provide strong evidence for associations between RSV disease severity and the presence of additional respiratory viruses and bacteria. The associations, while not indicating causation, are of potential clinical relevance. Awareness of coexisting microorganisms could inform therapeutic and preventive measures to improve the management and outcome of RSV-infected infants.

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Section: Introductionmentioning

confidence: 99%

Association between disease severity and co-detection of respiratory pathogens in infants with RSV infection

Lin

Drysdale

Snape

et al. 2023

Preprint

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“…After the manuscript submission a couple of articles appeared focusing on possible emerging epidemic threats, especially viruses coinfection, and new SARS-CoV-2 variants, indicating cutting edge research topics deserving attention. Haney et al 56 have conducted experiments on the coinfection of human lung cells with IAV and respiratory syncytial virus (RSV), finding the existence of hybrid virus particles (HVP) which are capable to evade anti-IAV neutralizing antibodies, thus defining in general an interaction between respiratory viruses such as SARS-CoV-2. Cao et al 57 have studied the evolution of the Omicron variant of SARS-CoV-2, demonstrating that mutations can evade neutralizing antibody drugs and convalescent plasma, suggesting that herd immunity and vaccine boosters could be inefficient to prevent infection from Omicron variants.…”

Section: Resultsmentioning

confidence: 99%

A mathematical model and numerical simulation for SARS-CoV-2 dynamics

Amoddeo

2023

Sci Rep

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Since its outbreak the corona virus-19 disease has been particularly aggressive for the lower respiratory tract, and lungs in particular. The dynamics of the abnormal immune response leading to lung damage with fatal outcomes is not yet fully understood. We present a mathematical model describing the dynamics of corona virus disease-19 starting from virus seeding inside the human respiratory tract, taking into account its interaction with the components of the innate immune system as classically and alternatively activated macrophages, interleukin-6 and -10. The numerical simulations have been performed for two different parameter values related to the pro-inflammatory interleukin, searching for a correlation among components dynamics during the early stage of infection, in particular pro- and anti-inflammatory polarizations of the immune response. We found that in the initial stage of infection the immune machinery is unable to stop or weaken the virus progression. Also an abnormal anti-inflammatory interleukin response is predicted, induced by the disease progression and clinically associated to tissue damages. The numerical results well reproduce experimental results found in literature.

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“…DCV may instead be benefiting from increased suppression of antiviral RNAi due to expression of the CrPV immune inhibitor [62], while CrPV is hindered by the activation of other mechanisms of host immunity by DCV. However, complex direct virus-virus interactions have been described in multiple coinfections, and it is possible that DCV and CrPV are directly influencing each other's expression or virion surface composition [93,94].…”

Section: Discussionmentioning

confidence: 99%

Investigating the outcomes of virus coinfection within and across host species

Imrie

Walsh

Roberts

et al. 2022

Preprint

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Interactions between coinfecting pathogens have the potential to alter the course of infection and can act as a source of phenotypic variation in susceptibility between hosts. This phenotypic variation may influence the evolution of host-pathogen interactions within host species and interfere with patterns in the outcomes of infection across host species. Here, we examine experimental coinfections of twoCripaviruses– Cricket Paralysis Virus (CrPV), and Drosophila C Virus (DCV) –across a panel of 25Drosophila melanogasterinbred lines and 47Drosophilidaehost species. We find that interactions between these viruses alter viral loads acrossD. melanogastergenotypes, with a ~3 fold increase in the viral load of DCV and a ~2.5 fold decrease in CrPV in coinfection compared to single infection, but we find little evidence of a host genetic basis for these effects. Across host species, we find no evidence of systematic changes in susceptibility during coinfection, with no interaction between DCV and CrPV detected in the majority of host species. These results suggest that phenotypic variation in coinfection interactions within host species can occur independently of natural host genetic variation in susceptibility, and that patterns of susceptibility across host species to single infections can be robust to the added complexity of coinfection.

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Coinfection by influenza A virus and respiratory syncytial virus produces hybrid virus particles

Cited by 45 publications

References 50 publications

Association between disease severity and co-detection of respiratory pathogens in infants with RSV infection

Association between disease severity and co-detection of respiratory pathogens in infants with RSV infection

A mathematical model and numerical simulation for SARS-CoV-2 dynamics

Investigating the outcomes of virus coinfection within and across host species

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