Network analysis of virus-innate immune interaction within a host

Huang, Yufan; Dai, Michelle; Zhang, Zhihao; Ke, Ruian

doi:10.1109/ciss.2018.8362278

Cited by 3 publications

(8 citation statements)

References 16 publications

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“…In this case, the infection threshold becomes much larger than the threshold in the absence of IFN response, suggesting that IFN can prevent virus infection (the green line in Figure 2A). As we showed previously, IFNs inhibit viral spread effectively when IFNs reach the same subset of cells as viruses and thus reduce the number of susceptible cells that an infected cell can infect (20). Interestingly, these conclusions are similar to those in a previous network modeling work analyzing the impact of the spread of epidemic awareness on the transmission of infectious diseases (21).…”

Section: Resultsmentioning

confidence: 68%

“…The network model with two ER graphs (results of the model with two independent layers are in red; results of the model with two identical layers are in yellow), and the network model with two GR networks (in black). Lines denote analytical results derived in Huang et al (20), whereas dots denote simulation results.…”

Section: Resultsmentioning

confidence: 99%

“…The average degrees in the infection layer and the protection layer are calculated as kI=(n-1)πrI 2≈ nπrI 2 and kF=(n-1)πrF 2≈ nπrF 2, respectively. Simulation procedures of the network models are described in Huang et al (20).…”

Section: Methodsmentioning

confidence: 99%

“…Note the expression is independent of parameter φ, i.e., the parameter for the impact of IFN on protecting target cells. The infection threshold β c of the network with two ER graphs and how it depends on the similarity between the two layers are derived previously in Huang et al (20).…”

Section: Methodsmentioning

confidence: 99%

“…We follow the derivations in Huang et al (20) to calculate the values of R I for the simulations with heterogenous infection rate. First, we calculate the probability that a susceptible cell become infected when it is connected to an infected cell in the infection layer.…”

Section: Methodsmentioning

confidence: 99%

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Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis

Huang

Dai

2019

Front. Immunol.

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The human innate immune response, particularly the type-I interferon (IFN) response, is highly robust and effective first line of defense against virus invasion. IFN molecules are produced and secreted from infected cells upon virus infection and recognition. They then act as signaling/communication molecules to activate an antiviral response in neighboring cells so that those cells become refractory to infection. Previous experimental studies have identified the detailed molecular mechanisms for the IFN signaling and response. However, the principles underlying how host cells use IFN to communicate with each other to collectively and robustly halt an infection is not understood. Here we take a multiplex network modeling approach to provide a theoretical framework to identify key factors that determine the effectiveness of the IFN response against virus infection of a host. In this approach, we consider the virus spread among host cells and the interferon signaling to protect host cells as a competition process on a two-layer multiplex network. We focused on two types of network topology, i.e., the Erdős-Rényi (ER) network and the Geometric Random (GR) network, which represent the scenarios when infection of cells is mostly well mixed (e.g., in the blood) and when infection is spatially segregated (e.g., in tissues), respectively. We show that in general, the IFN response works effectively to stop viral infection when virus infection spreads spatially (a most likely scenario for initial virus infection of a host at the peripheral tissue). Importantly, we show that the effectiveness of the IFN response is robust against large variations in the distance of IFN diffusion as long as IFNs diffuse faster than viruses and they can effectively induce antiviral responses in susceptible host cells. This suggests that the effectiveness of the IFN response is insensitive to the specific arrangement of host cells in peripheral tissues. Thus, our work provides a quantitative explanation of why the IFN response can serve an effective and robust response in different tissue types to a wide range of viral infections of a host.

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Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis

Huang

Dai

2019

Front. Immunol.

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

et al. 2021

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The innate immune response, particularly the interferon response, represents a first line of defence against viral infections. The interferon molecules produced from infected cells act through autocrine and paracrine signalling to turn host cells into an antiviral state. Although the molecular mechanisms of IFN signalling 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 signalling, 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 signalling is not as effective; by contrast, when infection spreads in a spatial manner, a likely scenario during initial infection in tissue, the paracrine signalling 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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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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Network analysis of virus-innate immune interaction within a host

Cited by 3 publications

References 16 publications

Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis

Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis

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

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

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