Antiviral interferon response at single‐cell resolution

Talemi, Soheil Rastgou; Höfer, Thomas

doi:10.1111/imr.12699

Cited by 26 publications

(29 citation statements)

References 69 publications

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“…Additionally, the distinct onsets of the IFN-I induction depend on the rapidity and amplitude of viral replication. This heterogeneous responsiveness at the individual cell level consequently shapes the dynamics of the host antiviral response at the whole population level [69][70][71]. This model of the IFN-I response dynamics yielded in the context of various RNA viruses provides a framework likely at play for coronavirus infections.…”

Section: Dynamics Of the Ifn-i Response At The Levels Of Individual Cmentioning

confidence: 96%

“…Studies at the single-cell level suggest that the amplitude and kinetic of the response is also heterogeneous for a given cell type. Mathematic modeling revealed that IFN-I response is, at least in part, stochastic because only a fraction of cells are able to produce IFN-I upon activation by agonists of the sensors and are sensitive to the paracrine stimulation by IFN-I [67][68][69][70][71]. The heterogeneity of the IFN-I response can be imprinted by the state of the cell at the activation time, including its global translation activity, metabolism, expression levels of signaling molecules (sensors, adaptors, and receptors) [67][68][69][70].…”

Section: Dynamics Of the Ifn-i Response At The Levels Of Individual Cmentioning

confidence: 99%

“…Mathematic modeling revealed that IFN-I response is, at least in part, stochastic because only a fraction of cells are able to produce IFN-I upon activation by agonists of the sensors and are sensitive to the paracrine stimulation by IFN-I [ 67 – 71 ]. The heterogeneity of the IFN-I response can be imprinted by the state of the cell at the activation time, including its global translation activity, metabolism, expression levels of signaling molecules (sensors, adaptors, and receptors) [ 67 – 70 ]. Additionally, the distinct onsets of the IFN-I induction depend on the rapidity and amplitude of viral replication.…”

Section: Dynamics Of the Ifn-i Response Define Severity Of Infectionmentioning

confidence: 99%

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Interplay between SARS-CoV-2 and the type I interferon response

et al. 2020

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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. An unbalanced immune response, characterized by a weak production of type I interferons (IFN-Is) and an exacerbated release of proinflammatory cytokines, contributes to the severe forms of the disease. SARS-CoV-2 is genetically related to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused outbreaks in 2003 and 2013, respectively. Although IFN treatment gave some encouraging results against SARS-CoV and MERS-CoV in animal models, its potential as a therapeutic against COVID-19 awaits validation. Here, we describe our current knowledge of the complex interplay between SARS-CoV-2 infection and the IFN system, highlighting some of the gaps that need to be filled for a better understanding of the underlying molecular mechanisms. In addition to the conserved IFN evasion strategies that are likely shared with SARS-CoV and MERS-CoV, novel counteraction mechanisms are being discovered in SARS-CoV-2-infected cells. Since the last coronavirus epidemic, we have made considerable progress in understanding the IFN-I response, including its spatiotemporal regulation and the prominent role of plasmacytoid dendritic cells (pDCs), which are the main IFN-I-producing cells. While awaiting the results of the many clinical trials that are evaluating the efficacy of IFN-I alone or in combination with antiviral molecules, we discuss the potential benefits of a well-timed IFN-I treatment and propose strategies to boost pDC-mediated IFN responses during the early stages of viral infection.

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Section: Dynamics Of the Ifn-i Response At The Levels Of Individual Cmentioning

confidence: 96%

Section: Dynamics Of the Ifn-i Response At The Levels Of Individual Cmentioning

confidence: 99%

Section: Dynamics Of the Ifn-i Response Define Severity Of Infectionmentioning

confidence: 99%

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Interplay between SARS-CoV-2 and the type I interferon response

et al. 2020

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“…This expression shows that the reduction of R 0 due to autocrine signaling is , where f is the inhibition of virus production due to the cellular antiviral response and k /( δ + k ) is the probability that an infected cell becomes antiviral by the autocrine pathway before cell death occurs In vitro experiments suggest that the fraction of infected cells that successfully enter an antiviral state is in general low [37, 38, 39], i.e. k /( δ + k ) is much less than 1.…”

Section: Resultsmentioning

confidence: 99%

Autocrine and paracrine interferon signaling as ‘ring vaccination’ and ‘contact tracing’ strategies to suppress virus infection in a host

Lavigne

Russell

Sherry

et al. 2020

Preprint

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The innate immune response, particularly the interferon response, represents a first line of defense against viral infections. The interferon molecules produced from infected cells act through autocrine and paracrine signaling to turn host cells into an antiviral state. Although the molecular mechanisms of IFN signaling have been well characterized, how the interferon response collectively contribute to the regulation of host cells to stop or suppress viral infection during early infection remain unclear. Here, we use mathematical models to delineate the roles of the autocrine and the paracrine signaling, and show that their impacts on viral spread are dependent on how infection proceeds. In particular, we found that when infection is well-mixed, the paracrine signaling is not as effective; in contrast, when infection spreads in a spatial manner, a likely scenario during initial infection in tissue, the paracrine signaling can impede the spread of infection by decreasing the number of susceptible cells close to the site of infection. Furthermore, we argue that the interferon response can be seen as a parallel to population-level epidemic prevention strategies such as contact tracing or ring vaccination. Thus, our results here may have implications for the outbreak control at the population scale more broadly.

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“…Here, it is clear that understanding the ongoing innate immune response may be critical to designing better treatment protocols. The theme of understanding the type I interferon response is continued in the review by Talemi & Höfer, where the tug of war between the antiviral interferon response and virus replication is described at the single cell level. At this level, the response is very heterogeneous and typically only 10%‐30% of cells in a population uniformly infected by virus express interferon‐β.…”

mentioning

confidence: 99%