| Title: |
A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in Uganda |
| Authors: |
Blanquart, F; Grabowski, MK; Herbeck, J; Nalugoda, F; Serwadda, D; Eller, MA; Robb, ML; Gray, R; Kigozi, G; Laeyendecker, O; Lythgoe, KA; Nakigozi, G; Quinn, TC; Reynolds, SJ; Wawer, MJ; Fraser, C |
| Contributors: |
Commission of the European Communities |
| Publisher Information: |
eLife Sciences Publications |
| Publication Year: |
2016 |
| Collection: |
Imperial College London: Spiral |
| Subject Terms: |
Science & Technology; Life Sciences & Biomedicine; Biology; Life Sciences & Biomedicine - Other Topics; GENITAL ULCER DISEASE; SIMPLEX-VIRUS TYPE-2; VIRAL LOAD; PROGNOSTIC MARKERS; PROSPECTIVE COHORT; SET-POINT; PROGRESSION; POPULATION; INFECTION; RAKAI; adaptation; epidemiology; evolutionary biology; genomics; global health; quantitative genetics; selection; transmission-virulence trade-off; viral evolution; virus |
| Description: |
Evolutionary theory hypothesizes that intermediate virulence maximizes pathogen fitness as a result of a trade-off between virulence and transmission, but empirical evidence remains scarce. We bridge this gap using data from a large and long-standing HIV-1 prospective cohort, in Uganda. We use an epidemiological-evolutionary model parameterised with this data to derive evolutionary predictions based on analysis and detailed individual-based simulations. We robustly predict stabilising selection towards a low level of virulence, and rapid attenuation of the virus. Accordingly, set-point viral load, the most common measure of virulence, has declined in the last 20 years. Our model also predicts that subtype A is slowly outcompeting subtype D, with both subtypes becoming less virulent, as observed in the data. Reduction of set-point viral loads should have resulted in a 20% reduction in incidence, and a three years extension of untreated asymptomatic infection, increasing opportunities for timely treatment of infected individuals. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
eLife; http://hdl.handle.net/10044/1/48184; https://dx.doi.org/10.7554/eLife.20492; 339251; 657768 |
| DOI: |
10.7554/eLife.20492 |
| Availability: |
http://hdl.handle.net/10044/1/48184; https://doi.org/10.7554/eLife.20492 |
| Rights: |
© 2016 Blanquart et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. |
| Accession Number: |
edsbas.E7D2EC7F |
| Database: |
BASE |