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Causes and Consequences of Spatial Within-Host Viral Spread

Department of Biology, Emory University, Atlanta, GA 30322, USA
Department of Microbiology, University of Illinois at Urbana-Champaign, Champaign, IL 61801, USA
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Champaign, IL 61801, USA
T-6, Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
Author to whom correspondence should be addressed.
Viruses 2018, 10(11), 627;
Received: 28 September 2018 / Revised: 8 November 2018 / Accepted: 10 November 2018 / Published: 13 November 2018
(This article belongs to the Special Issue What’s New with Flu?)
The spread of viral pathogens both between and within hosts is inherently a spatial process. While the spatial aspects of viral spread at the epidemiological level have been increasingly well characterized, the spatial aspects of viral spread within infected hosts are still understudied. Here, with a focus on influenza A viruses (IAVs), we first review experimental studies that have shed light on the mechanisms and spatial dynamics of viral spread within hosts. These studies provide strong empirical evidence for highly localized IAV spread within hosts. Since mathematical and computational within-host models have been increasingly used to gain a quantitative understanding of observed viral dynamic patterns, we then review the (relatively few) computational modeling studies that have shed light on possible factors that structure the dynamics of spatial within-host IAV spread. These factors include the dispersal distance of virions, the localization of the immune response, and heterogeneity in host cell phenotypes across the respiratory tract. While informative, we find in these studies a striking absence of theoretical expectations of how spatial dynamics may impact the dynamics of viral populations. To mitigate this, we turn to the extensive ecological and evolutionary literature on range expansions to provide informed theoretical expectations. We find that factors such as the type of density dependence, the frequency of long-distance dispersal, specific life history characteristics, and the extent of spatial heterogeneity are critical factors affecting the speed of population spread and the genetic composition of spatially expanding populations. For each factor that we identified in the theoretical literature, we draw parallels to its analog in viral populations. We end by discussing current knowledge gaps related to the spatial component of within-host IAV spread and the potential for within-host spatial considerations to inform the development of disease control strategies. View Full-Text
Keywords: Influenza virus; within-host viral dynamics; spatial spread; within-host evolution Influenza virus; within-host viral dynamics; spatial spread; within-host evolution
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MDPI and ACS Style

Gallagher, M.E.; Brooke, C.B.; Ke, R.; Koelle, K. Causes and Consequences of Spatial Within-Host Viral Spread. Viruses 2018, 10, 627.

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