The Library
Large variations in HIV-1 viral load explained by shifting-mosaic metapopulation dynamics
Tools
Lythgoe, Katrina A., Blanquart, François, Pellis, Lorenzo and Fraser, Christophe (2016) Large variations in HIV-1 viral load explained by shifting-mosaic metapopulation dynamics. PLoS Biology, 14 (10). e1002567. doi:10.1371/journal.pbio.1002567 ISSN 1545-7885.
PDF
WRAP_journal.pbio.1002567.PDF - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2785Kb) |
Official URL: http://dx.doi.org/10.1371/journal.pbio.1002567
Abstract
The viral population of HIV-1, like many pathogens that cause systemic infection, is structured and differentiated within the body. The dynamics of cellular immune trafficking through the blood and within compartments of the body has also received wide attention. Despite these advances, mathematical models, which are widely used to interpret and predict viral and immune dynamics in infection, typically treat the infected host as a well-mixed homogeneous environment. Here, we present mathematical, analytical, and computational results that demonstrate that consideration of the spatial structure of the viral population within the host radically alters predictions of previous models. We study the dynamics of virus replication and cytotoxic T lymphocytes (CTLs) within a metapopulation of spatially segregated patches, representing T cell areas connected by circulating blood and lymph. The dynamics of the system depend critically on the interaction between CTLs and infected cells at the within-patch level. We show that for a wide range of parameters, the system admits an unexpected outcome called the shifting-mosaic steady state. In this state, the whole body’s viral population is stable over time, but the equilibrium results from an underlying, highly dynamic process of local infection and clearance within T-cell centers. Notably, and in contrast to previous models, this new model can explain the large differences in set-point viral load (SPVL) observed between patients and their distribution, as well as the relatively low proportion of cells infected at any one time, and alters the predicted determinants of viral load variation.
Item Type: | Journal Article | ||||||||
---|---|---|---|---|---|---|---|---|---|
Subjects: | Q Science > QR Microbiology > QR355 Virology | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Mathematics | ||||||||
Library of Congress Subject Headings (LCSH): | HIV (Viruses) , Mathematical models, Lymph, Blood | ||||||||
Journal or Publication Title: | PLoS Biology | ||||||||
Publisher: | Public Library of Science | ||||||||
ISSN: | 1545-7885 | ||||||||
Official Date: | 5 October 2016 | ||||||||
Dates: |
|
||||||||
Volume: | 14 | ||||||||
Number: | 10 | ||||||||
Article Number: | e1002567 | ||||||||
DOI: | 10.1371/journal.pbio.1002567 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 27 October 2016 | ||||||||
Date of first compliant Open Access: | 28 October 2016 | ||||||||
Funder: | Sir Henry Dale Fellowship, Marie Curie Individual Fellowship, Engineering and Physical Sciences Research Council (EPSRC), European Research Council (ERC) | ||||||||
Grant number: | 107652 (Sir Henry Dale Fellowship), 657768 (Marie Cure), EP/J002437/1 (ESRC), 339251 (ERC) |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year