Detection of respiratory syncytial virus defective genomes in nasal secretions is associated with distinct clinical outcomes

Felt, Sébastien A.; Sun, Yan; Jóźwik, Agnieszka; Paras, Allan; Habibi, Maximillian S.; Nickle, David C.; Anderson, Larry J.; Achouri, Emna; Feemster, Kristen A.; Cárdenas, Ana Marı́a; Turi, Kedir N.; Chang, Min S.; Hartert, Tina V.; Sengupta, Shaon; Chiu, Christopher; López, Carolina B.

doi:10.1038/s41564-021-00882-3

Cited by 45 publications

(62 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DVGs detected early in the course of infection were associated with mild disease, and DVGs detected later were linked to severe disease. Patients with DVGs had heightened expression of cytokines, including IFN alpha, which aligned with past studies linking induction of IFN to DVGs and DIPs [137].…”

Section: Dips and The Immune Responsesupporting

confidence: 80%

Virus-like Particles: Measures and Biological Functions

Bhat

Cao

Yin

2022

Viruses

View full text Add to dashboard Cite

Virus-like particles resemble infectious virus particles in size, shape, and molecular composition; however, they fail to productively infect host cells. Historically, the presence of virus-like particles has been inferred from total particle counts by microscopy, and infectious particle counts or plaque-forming-units (PFUs) by plaque assay; the resulting ratio of particles-to-PFUs is often greater than one, easily 10 or 100, indicating that most particles are non-infectious. Despite their inability to hijack cells for their reproduction, virus-like particles and the defective genomes they carry can exhibit a broad range of behaviors: interference with normal virus growth during co-infections, cell killing, and activation or inhibition of innate immune signaling. In addition, some virus-like particles become productive as their multiplicities of infection increase, a sign of cooperation between particles. Here, we review established and emerging methods to count virus-like particles and characterize their biological functions. We take a critical look at evidence for defective interfering virus genomes in natural and clinical isolates, and we review their potential as antiviral therapeutics. In short, we highlight an urgent need to better understand how virus-like genomes and particles interact with intact functional viruses during co-infection of their hosts, and their impacts on the transmission, severity, and persistence of virus-associated diseases.

show abstract

Section: Dips and The Immune Responsesupporting

confidence: 80%

Virus-like Particles: Measures and Biological Functions

Bhat

Cao

Yin

2022

Viruses

View full text Add to dashboard Cite

show abstract

“…[ 11 ] However, clinical sequencing has revealed that they are a common component of viral infections and can be associated with disease outcome. [ 12 – 14 ] Their potential ability to modulate the course of disease has now sparked a renewed interest in their therapeutic potential. [ 15 – 18 ]…”

Section: Introductionmentioning

confidence: 99%

Library-based analysis reveals segment and length dependent characteristics of defective influenza genomes

Mendes

Russell

2021

PLoS Pathog

View full text Add to dashboard Cite

Found in a diverse set of viral populations, defective interfering particles are parasitic variants that are unable to replicate on their own yet rise to relatively high frequencies. Their presence is associated with a loss of population fitness, both through the depletion of key cellular resources and the stimulation of innate immunity. For influenza A virus, these particles contain large internal deletions in the genomic segments which encode components of the heterotrimeric polymerase. Using a library-based approach, we comprehensively profile the growth and replication of defective influenza species, demonstrating that they possess an advantage during genome replication, and that exclusion during population expansion reshapes population composition in a manner consistent with their final, observed, distribution in natural populations. We find that an innate immune response is not linked to the size of a deletion; however, replication of defective segments can enhance their immunostimulatory properties. Overall, our results address several key questions in defective influenza A virus biology, and the methods we have developed to answer those questions may be broadly applied to other defective viruses.

show abstract

“…DIPs have been demonstrated in numerous contexts to interfere with wild-type (WT) virus replication (hence the name), ostensibly either by outcompeting wild-type genomes for replication and packaging and/or by triggering innate immune activation ( 3 – 7 ). Recent studies have correlated the abundance of DIPs within clinical samples with severity of both IAV and respiratory syncytial virus infection, suggesting a role for DIPs in modulating viral pathogenicity ( 8 , 9 ). Despite being discovered over 60 years ago, the specific molecular processes that drive DIP formation, as well as the effects of DIPs on the collective behavior and pathogenicity of viral populations, remain mysterious ( 10 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

Influenza A Virus Defective Viral Genomes Are Inefficiently Packaged into Virions Relative to Wild-Type Genomic RNAs

Alnaji

Reiser

Rivera-Cardona

et al. 2021

mBio

View full text Add to dashboard Cite

show abstract

Detection of respiratory syncytial virus defective genomes in nasal secretions is associated with distinct clinical outcomes

Abstract: The kinetics of defective viral genomes appearance during infection with RSV determines the clinical outcome of the infection.

Cited by 45 publications

References 54 publications

Virus-like Particles: Measures and Biological Functions

Virus-like Particles: Measures and Biological Functions

Library-based analysis reveals segment and length dependent characteristics of defective influenza genomes

Influenza A Virus Defective Viral Genomes Are Inefficiently Packaged into Virions Relative to Wild-Type Genomic RNAs

Contact Info

Product

Resources

About