Quasineutral multistability in an epidemiological-like model for defective-helper betacoronavirus infection in cell cultures DOI Creative Commons
Juan C. Muñoz-Sánchez, J. Tomás Lázaro, Julia Hillung

et al.

Applied Mathematical Modelling, Journal Year: 2024, Volume and Issue: 137, P. 115673 - 115673

Published: Sept. 3, 2024

It is well known that, during replication, RNA viruses spontaneously generate defective viral genomes (DVGs). DVGs are unable to complete an infectious cycle autonomously and depend on coinfection with a wild-type helper virus (HV) for their replication and/or transmission. The study of the dynamics arising from HV its has been longstanding question in virology. shown that can modulate and, depending strength interference, result extinctions or self-sustained persistent fluctuations. Extensive experimental work provided mechanistic explanations DVG generation compelling evidences HV-DVGs coevolution. Some these observations have captured by mathematical models. Here, we develop investigate epidemiological-like model specifically designed betacoronavirus cell culture experiments. governed several degenerate normally hyperbolic invariant manifolds given quasineutral planes - i.e., filled equilibrium points. Three different identified parameters involving: (i) persistence DVGs; (ii) non-infected cells DVG-infected cells; (iii) DVGs. Key involved scenarios maximum burst size (B), fraction produced (β), advantage (δ). More precisely, case 01+β+δ, becomes globally attractor. Scenarios compatible so-called self-curing since removed population. Sensitivity analyses indicate largely production rate (β) replicative (δ), both infection rates virus-induced deaths. Finally, fitted single-passage data using artificial intelligence methodology based genetic algorithms key virological estimated.

Language: Английский

The role of trained immunity in COVID-19: Lessons for the next pandemic DOI Creative Commons

Mihai G. Netea,

Athanasios Ziogas, Christine Stabell Benn

et al.

Cell Host & Microbe, Journal Year: 2023, Volume and Issue: 31(6), P. 890 - 901

Published: June 1, 2023

Language: Английский

Citations

37
Generation and Functional Analysis of Defective Viral Genomes during SARS-CoV-2 Infection DOI Creative Commons

Terry Zhou,

Nora J. Gilliam,

Sizhen Li

et al.

mBio, Journal Year: 2023, Volume and Issue: 14(3)

Published: April 19, 2023

Defective viral genomes (DVGs) are generated ubiquitously in many RNA viruses, including SARS-CoV-2. Their interference activity to full-length viruses and IFN stimulation provide the potential for them be used novel antiviral therapies vaccine development.

Language: Английский

Citations

28
Defective viral genomes: advances in understanding their generation, function, and impact on infection outcomes DOI Creative Commons
Justin W. Brennan, Yan Sun

mBio, Journal Year: 2024, Volume and Issue: 15(5)

Published: April 3, 2024

ABSTRACT Defective viral genomes (DVGs) are truncated derivatives of their parental generated during an aberrant round genomic replication. Distinct classes DVGs have been identified in most families both positive- and negative-sense RNA viruses. Importantly, detected clinical samples from virally infected individuals emerging body association studies implicates shaping the severity disease caused by infections humans. Consequently, there is growing interest understanding molecular mechanisms de novo DVG generation, how interact with innate immune system, harnessing as novel therapeutics vaccine adjuvants to attenuate pathogenesis. This minireview focuses on single-stranded viruses (excluding retroviridae), summarizes current knowledge functions diversity species, roles play influencing progression, application antivirals adjuvants.

Language: Английский

Citations

10
Exploring enterovirus pathogenesis and cancer therapy potential through reverse genetics DOI Creative Commons
Shijin Wang, Qinghua Yu,

Zhou Junfeng

et al.

Biosafety and Health, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Virus-like Particles: Measures and Biological Functions DOI Creative Commons
Tara Bhat,

Amy Cao,

John Yin

et al.

Viruses, Journal Year: 2022, Volume and Issue: 14(2), P. 383 - 383

Published: Feb. 14, 2022

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

Language: Английский

Citations

38
Evolutionary implications of SARS-CoV-2 vaccination for the future design of vaccination strategies DOI Creative Commons
Igor M. Rouzine, Ganna Rozhnova

Communications Medicine, Journal Year: 2023, Volume and Issue: 3(1)

Published: June 19, 2023

Once the first SARS-CoV-2 vaccine became available, mass vaccination was main pillar of public health response to COVID-19 pandemic. It very effective in reducing hospitalizations and deaths. Here, we discuss possibility that might accelerate evolution antibody-binding regions compared natural infection at population level. Using evidence strong genetic variation taking advantage similarity between envelope proteins influenza, assume immune selection pressure acting on these two viruses is similar. We consequences this assumption for light mathematical models developed previously influenza. further outline implications phenomenon, if our assumptions are confirmed, future design strategies.

Language: Английский

Citations

22
Cryptic proteins translated from deletion-containing viral genomes dramatically expand the influenza virus proteome DOI Creative Commons
Jordan N Ranum,

Mitchell P. Ledwith,

Fadi G. Alnaji

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(6), P. 3199 - 3212

Published: Feb. 26, 2024

Abstract Productive infections by RNA viruses require faithful replication of the entire genome. Yet many also produce deletion-containing viral genomes (DelVGs), aberrant products with large internal deletions. DelVGs interfere wild-type virus and their presence in patients is associated better clinical outcomes. The DelVG itself hypothesized to confer this interfering activity. antagonize out-competing full-length genome triggering innate immune responses. Here, we identify an additionally inhibitory mechanism mediated a new class proteins encoded DelVGs. We identified hundreds cryptic translated from These DelVG-encoded (DPRs) include canonical deletions, as well novel C-termini alternative reading frames. Many DPRs retain functional domains shared counterparts, suggesting they may have activity during infection. Mechanistic studies derived influenza protein PB2 showed that poison acting dominant-negative inhibitors polymerase. findings reveal dual mechanism, at both level. They further show potential dramatically expand proteomes diverse viruses.

Language: Английский

Citations

6
Evolution of naturally arising SARS-CoV-2 defective interfering particles DOI Creative Commons

Samer Girgis,

Zaikun Xu,

Spyros Oikonomopoulos

et al.

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: Oct. 27, 2022

Abstract Defective interfering (DI) particles arise during virus propagation, are conditional on parental for replication and packaging, interfere with viral expansion. There is much interest in developing DIs as anti-viral agents. Here we characterize DI that arose following serial passaging of SARS-CoV-2 at high multiplicity infection. The prominent identified have lost ~84% the genome capable attenuating titers. Synthetic variants genomes also infection can be used conditional, gene delivery vehicles. In addition, encode an Nsp1-10 fusion protein replication. These results identify naturally selected defective emerged stably propagated presence virus.

Language: Английский

Citations

28
The Nucleocapsid Protein of SARS-CoV-2, Combined with ODN-39M, Is a Potential Component for an Intranasal Bivalent Vaccine with Broader Functionality DOI Creative Commons
Yadira Lobaina, Rong Chen, Edith Suzarte

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(3), P. 418 - 418

Published: March 8, 2024

Despite the rapid development of vaccines against COVID-19, they have important limitations, such as safety issues, scope their efficacy, and induction mucosal immunity. The present study proposes a potential component for new generation vaccines. recombinant nucleocapsid (N) protein from SARS-CoV-2 Delta variant was combined with ODN-39M, synthetic 39 mer unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN), used an adjuvant. evaluation its immunogenicity in Balb/C mice revealed that only administration by intranasal route induced systemic cross-reactive, cell-mediated immunity (CMI). In turn, this combination able to induce anti-N IgA lungs, which, along specific IgG sera CMI spleen, cross-reactive SARS-CoV-1. Furthermore, nasal N + ODN-39M preparation, RBD protein, enhanced local immune response RBD, neutralizing capacity. Results make preparation suitable future vaccine broader functionality Sarbecoviruses.

Language: Английский

Citations

6
Selection of nonstandard viral genomes during the evolution of RNA viruses: A virus survival strategy or a pesky inconvenience? DOI
Lavinia J. González Aparicio, Carolina B. López

Advances in virus research, Journal Year: 2024, Volume and Issue: unknown, P. 39 - 61

Published: Jan. 1, 2024

Language: Английский

Citations

6