Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01736/full |
| _version_ | 1818062352403136512 |
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| author | Yufan Huang Huaiyu Dai Ruian Ke Ruian Ke |
| author_facet | Yufan Huang Huaiyu Dai Ruian Ke Ruian Ke |
| author_sort | Yufan Huang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T14:02:51Z |
| format | Article |
| id | doaj.art-32af32bd28084865adffabbac4cffba1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T14:02:51Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-32af32bd28084865adffabbac4cffba12022-12-22T01:45:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-07-011010.3389/fimmu.2019.01736439875Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network AnalysisYufan Huang0Huaiyu Dai1Ruian Ke2Ruian Ke3Department of Electrical and Computer Engineering, North Carolina State University, Raleigh, NC, United StatesDepartment of Electrical and Computer Engineering, North Carolina State University, Raleigh, NC, United StatesDepartment of Mathematics, North Carolina State University, Raleigh, NC, United StatesT-6, Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, United StatesThe 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.01736/fullimmune responseinterferonviral infectionmathematical modelingmultiplex network |
| spellingShingle | Yufan Huang Huaiyu Dai Ruian Ke Ruian Ke Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis Frontiers in Immunology immune response interferon viral infection mathematical modeling multiplex network |
| title | Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis |
| title_full | Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis |
| title_fullStr | Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis |
| title_full_unstemmed | Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis |
| title_short | Principles of Effective and Robust Innate Immune Response to Viral Infections: A Multiplex Network Analysis |
| title_sort | principles of effective and robust innate immune response to viral infections a multiplex network analysis |
| topic | immune response interferon viral infection mathematical modeling multiplex network |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01736/full |
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