Effect of the latent reservoir on the evolution of HIV at the within- and between-host Levels
File(s)
Published version
Author(s)
Doekes, HM
Fraser, C
Lythgoe, KA
Type
Journal Article
Abstract
The existence of long-lived reservoirs of latently infected CD4+ T cells is the major barrier to curing HIV, and has been extensively studied in this light. However, the effect of these reservoirs on the evolutionary dynamics of the virus has received little attention. Here, we present a within-host quasispecies model that incorporates a long-lived reservoir, which we then nest into an epidemiological model of HIV dynamics. For biologically plausible parameter values, we find that the presence of a latent reservoir can severely delay evolutionary dynamics within a single host, with longer delays associated with larger relative reservoir sizes and/or homeostatic proliferation of cells within the reservoir. These delays can fundamentally change the dynamics of the virus at the epidemiological scale. In particular, the delay in within-host evolutionary dynamics can be sufficient for the virus to evolve intermediate viral loads consistent with maximising transmission, as is observed, and not the very high viral loads that previous models have predicted, an effect that can be further enhanced if viruses similar to those that initiate infection are preferentially transmitted. These results depend strongly on within-host characteristics such as the relative reservoir size, with the evolution of intermediate viral loads observed only when the within-host dynamics are sufficiently delayed. In conclusion, we argue that the latent reservoir has important, and hitherto under-appreciated, roles in both within- and between-host viral evolution.
Date Issued
2017-01-19
Date Acceptance
2016-10-31
Citation
PLoS Computational Biology, 2017, 13 (1), pp.1-27
ISSN
1553-734X
Publisher
Public Library of Science (PLoS)
Start Page
1
End Page
27
Journal / Book Title
PLoS Computational Biology
Volume
13
Issue
1
Copyright Statement
© 2017 Doekes et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited. : Doekes HM, Fraser C, Lythgoe KA (2017)
Effect of the Latent Reservoir on the Evolution of
HIV at the Within- and Between-Host Levels. PLoS Comput Biol 13(1): e1005228. doi:10.1371/journal.
pcbi.1005228
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited. : Doekes HM, Fraser C, Lythgoe KA (2017)
Effect of the Latent Reservoir on the Evolution of
HIV at the Within- and Between-Host Levels. PLoS Comput Biol 13(1): e1005228. doi:10.1371/journal.
pcbi.1005228
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000394144400005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemical Research Methods
Mathematical & Computational Biology
Biochemistry & Molecular Biology
HUMAN-IMMUNODEFICIENCY-VIRUS
ACTIVE ANTIRETROVIRAL THERAPY
CD4(+) T-CELLS
VIRAL LOAD
IN-VIVO
DISEASE PROGRESSION
WITHIN-HOST
HIV-1-INFECTED PATIENTS
GENETIC DIVERSITY
TYPE-1 FITNESS
Publication Status
Published
Article Number
ARTN e1005228