A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in uganda

François Blanquart; Mary Kate Grabowski; Joshua Herbeck; Fred Nalugoda; David Serwadda; Michael A. Eller; Merlin L. Robb; Ronald Gray; Godfrey Kigozi; Oliver Laeyendecker; Katrina A. Lythgoe; Gertrude Nakigozi; Thomas C. Quinn; Steven J. Reynolds; Maria J. Wawer; Christophe Fraser

doi:10.7554/eLife.20492

A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in uganda

François Blanquart, Mary Kate Grabowski, Joshua Herbeck, Fred Nalugoda, David Serwadda, Michael A. Eller, Merlin L. Robb, Ronald Gray, Godfrey Kigozi, Oliver Laeyendecker, Katrina A. Lythgoe, Gertrude Nakigozi, Thomas C. Quinn, Steven J. Reynolds, Maria J. Wawer, Christophe Fraser

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21 Scopus citations

Abstract

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.

Original language	English (US)
Article number	e20492
Journal	eLife
Volume	5
Issue number	NOVEMBER2016
DOIs	https://doi.org/10.7554/eLife.20492
State	Published - Nov 5 2016

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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10.7554/eLife.20492

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Blanquart, F., Grabowski, M. K., Herbeck, J., Nalugoda, F., Serwadda, D., Eller, M. A., Robb, M. L., Gray, R., Kigozi, G., Laeyendecker, O., Lythgoe, K. A., Nakigozi, G., Quinn, T. C., Reynolds, S. J., Wawer, M. J., & Fraser, C. (2016). A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in uganda. eLife, 5(NOVEMBER2016), Article e20492. https://doi.org/10.7554/eLife.20492

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 2016, 'A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in uganda', eLife, vol. 5, no. NOVEMBER2016, e20492. https://doi.org/10.7554/eLife.20492

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abstract = "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.",

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AU - Eller, Michael A.

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AU - Laeyendecker, Oliver

AU - Lythgoe, Katrina A.

AU - Nakigozi, Gertrude

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AU - Reynolds, Steven J.

AU - Wawer, Maria J.

AU - Fraser, Christophe

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A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in uganda

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