Influenza viruses and coronaviruses: Knowns, unknowns, and common research challenges

Terrier, B.; Si‐Tahar, Mustapha; Ducatez, Mariette; Chevalier, Christophe; Pizzorno, Andrés; Goffic, Ronan Le; Crépin, Thibaut; Simon, Gaëlle; Naffakh, Nadia

doi:10.1371/journal.ppat.1010106

Cited by 15 publications

(16 citation statements)

References 178 publications

(195 reference statements)

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“…Respiratory RNA viruses have been linked to a variety of illnesses. Influenza viruses and coronaviruses are two major respiratory viruses with pandemic potential [ 56 , 57 ]. COVID-19 is a worldwide public health emergency concern, and the increasing number of cases of this highly transmissible infection has highlighted the urgent need to find a satisfactory treatment [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions

et al. 2022

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Controlling the infectivity of respiratory RNA viruses is critical, especially during the current SARS-CoV-2 pandemic. There is an unmet need for therapeutic agents that can reduce viral replication, preferably independent of the accumulation of viral mutations. Zinc ions have an apparent activity as modulators of intracellular viral RNA replication and thus, appear attractive in reducing viral RNA load and infectivity. However, the intracellular concentration of zinc is usually too low for achieving an optimal inhibitory effect. Various herbal polyphenols serve as excellent zinc ionophores with known antiviral properties. Here, we combined zinc picolinate with a collection of flavonoids, representing commonly used polyphenols. Copper was added to avoid ionic imbalance during treatment and to improve efficacy. Each component separately, as well as their combinations, did not interfere with the viability of cultured A549, H1299, or Vero cells in vitro as determined by MTT assay. The safe combinations were further evaluated to determine antiviral activity. Fluorescence-activated cell sorting and quantitative polymerase chain reaction were used to evaluate antiviral activity of the combinations. They revealed a remarkable (50–95%) decrease, in genome replication levels of a diverse group of respiratory RNA viruses, including the human coronavirus OC43 (HCoV-OC43; a betacoronavirus that causes the common cold), influenza A virus (IAV, strain A/Puerto Rico/8/34 H1N1), and human metapneumovirus (hMPV). Collectively, our results offer an orally bioavailable therapeutic approach that is non-toxic, naturally sourced, applicable to numerous RNA viruses, and potentially insensitive to new mutations and variants.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions

et al. 2022

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“…The global spread of viral pathogens, such as IAV and SARS-CoV-2, led to major economic and health challenges worldwide [42][43][44]. Revealing host genes essential for infection by IAV can provide insights into the virus pathogenesis, and facilitate the development of novel therapeutics.…”

Section: Discussionmentioning

confidence: 99%

TREX (transcription/export)-NP complex exerts a dual effect on regulating polymerase activity and replication of influenza A virus

et al. 2022

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Influenza A viruses effectively hijack the intracellular "resources" to complete transcription and replication, which involve extensive interactions between the viral and host proteins. Herein, we screened the host factors, which belong to DExD/H-box protein family members, RNA-binding proteins or mitochondrial anchoring proteins, to investigate their effects on polymerase activity. We observed DDX39B and DDX39A, DEAD-box RNA-Helicases, exert a dual effect on regulating polymerase activity and replication of influenza A viruses. We further revealed that DDX39B and DDX39A interact with viral NP and NS1 proteins. Interestingly, the viral NP proteins could reverse the inhibitory effect of excess DDX39B or DDX39A on polymerase activity. Mechanistically, the TREX complex subunits, THOC1, THOC4 and CIP29, were recruited to DDX39B-DDX39A-NP complex in an ATP-dependent manner, via the interaction with DDX39B or DDX39A, followed by excess TREX-NP complexes interfere with the normal oligomerization state of NP depending on the ratio between the viral and host proteins. On the other hand, the TREX complex, an evolutionarily conserved protein complex, is responsible for the integration of several mRNA processing steps to export viral mRNA. Knockdown of TREX complex subunits significantly down-regulated viral titers and protein levels, accompanied by retention of viral mRNA in the nucleus. Taken together, screening the host factors that regulate the replication of influenza virus advances our understanding of viral pathogenesis and our findings point out a previously unclear mechanism of TREX complex function.

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“…These findings support our operationalized within-host concept at a population level. Within-host seasonal immunity is a rather unspecified concept and the lack of knowledge on how the seasonality of these genes changes the immune system is challenging (1, 2, 5, 8). The applied definition of both a seasonal term and a flu term in the model could be one way of searching for genes participating in within-host seasonal immunity.…”

Section: Discussionmentioning

confidence: 99%

“…The seasonality of covid-19 is clearly demonstrated in the Norwegian number of deaths for the period February 2020 till January 2022, Figure 1 (6). The two diseases share the common nature of being mRNA virus but with important differences like influenza virus with negative sense and coronavirus with positive sense, among others (7, 8). These are two of the major zoonotic respiratory viruses with capabilities of a pandemic spread.…”

Section: Introductionmentioning

confidence: 99%

Trajectories of gene expression, seasonal influenza, and within-host seasonal immunity: transfer value to covid-19

Lund

Holden

Busund

et al. 2022

Preprint

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As a novel approach we will combine trajectories or longitudinal studies of gene expression with information on annual influenza epidemics. Seasonality of gene expression in immune cells from blood could be a consequence of within-host seasonal immunity interacting with the seasonal pandemics of influenza (flu) in temperate regions and, thus, with potential valuable analogy transfer to the proposed seasonal development of covid-19.Here we operationalized within-host immunity as genes with both a significant seasonal term and a significant flu term in the sine-cosine model. Information on gene expression was based on microarray using RNase buffered blood samples collected randomly from a population-based cohort of Norwegian middle-aged women in 2003-2006, The Norwegian Women and Cancer (NOWAC) study. The unique discovery (N=425) and replication (N=432) design were based on identical sampling and preprocessing. Data on proportion of sick leaves due to flu, and the flu intensities per week was obtained from the National Institute of Public Health, giving a semi-ecological analysis.The discovery analysis found 2942 (48.1%) significant genes in a generalized seasonal model over four years. For 1051 within-host genes both the seasonal and the flu term were significant. These genes followed closely the flu intensities. The trajectories showed slightly more genes with a maximum in early winter than in late summer. Moving the flu intensity forward in time indicated a better fit 3-4 weeks before the observed influenza. In the replication analyses, 369 genes (35.1% of 1051) were significant. Exclusion of genes with unknown functions and with more than a season in difference reduced the number of genes in the discovery dataset to 305, illustrating the variability in the measurements and the problem in assessing weak biological relationships. Thus, we found for the first time a clear seasonality in gene expression with marked responses to the annual seasonal influenza in a unique discovery – replication design. Hypothetically, this could support the within-host seasonal immunity concept.

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Influenza viruses and coronaviruses: Knowns, unknowns, and common research challenges

Cited by 15 publications

References 178 publications

Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions

Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions

TREX (transcription/export)-NP complex exerts a dual effect on regulating polymerase activity and replication of influenza A virus

Trajectories of gene expression, seasonal influenza, and within-host seasonal immunity: transfer value to covid-19

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