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

Abstract

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.

Generation of multicellular spatiotemporal models of population dynamics from ordinary differential equations, with applications in viral infection

“…Spread of viral pathogens during infection is well known to be an inherently spatial process, though the spatiotemporal details of viral spread have not been well studied [ 22 ]. Recent computational modeling and simulation have shown the critical importance of considering spatial spread of infection when studying immune response mechanisms like autocrine and paracrine interferon signaling [ 23 ], while recent single-cell transcriptomics has shown the significance of cellular heterogeneity in the innate immune response to influenza A virus [ 24 ]. In this section, we demonstrate the cellularization of ODE models of viral infection and immune response according to the formalism defined in “Conclusion.”…”

Modeling suggests that multiple immunizations or infections will reveal the benefits of updating SARS-CoV-2 vaccines

“…These would include different populations of dendritic cells, follicular CD4 T cells, as well as different populations of B cells and plasma cells ( 33, 34, 44 – 50 ). Further complexities specific to CoV-2 include the spatial aspect of infections of the respiratory tract ( 51 – 54 ) as well as the dynamics of production and distribution of antigen by mRNA based vaccines ( 55 ) as well as infections. As more data becomes available, it will be possible to construct more nuanced and refined models of the dynamics of humoral immunity as well as affinity maturation ( 56 – 62 ).…”

Forms and Methods for Interferon's Encapsulation

“…In an uninfected cell, binding of IFN to its receptor and subsequent IFN signaling renders the cell refractory to viral infection. In an infected cell, this signaling can suppress viral replication and decrease the release of viral progeny from the cell [148]. During initial infection in tissue, paracrine signaling can prevent the spread of infection by reducing the number of susceptible cells near the site of infection [149].…”