Evolution during primary HIV infection does not require adaptive immune selection

Modern HIV research depends crucially on both viral sequencing and population measurements. To directly link mechanistic biological processes and evolutionary dynamics during HIV infection, we developed multiple within-host phylodynamic models of HIV primary infection for comparative validation agai...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2022-02, Vol.119 (7)
Main Authors: Swan, David A, Rolland, Morgane, Herbeck, Joshua T, Schiffer, Joshua T, Reeves, Daniel B
Format: Article
Language:English
Subjects:
Adaptation, Physiological - genetics
Adaptive immunity
Adaptive systems
Biological activity
Biological Sciences
Evolution
Fitness
Genetic Fitness
HIV
HIV Infections - virology
HIV-1 - genetics
Human immunodeficiency virus
Humans
Immune system
Infections
Infectivity
Models, Genetic
Mutation
Phylogenetics
Phylogeny
Physical Sciences
Positive selection
Probability distribution functions
Reproducibility of Results
Reproductive fitness
Viral Load
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Summary:Modern HIV research depends crucially on both viral sequencing and population measurements. To directly link mechanistic biological processes and evolutionary dynamics during HIV infection, we developed multiple within-host phylodynamic models of HIV primary infection for comparative validation against viral load and evolutionary dynamics data. The optimal model of primary infection required no positive selection, suggesting that the host adaptive immune system reduces viral load but surprisingly does not drive observed viral evolution. Rather, the fitness (infectivity) of mutant variants is drawn from an exponential distribution in which most variants are slightly less infectious than their parents (nearly neutral evolution). This distribution was not largely different from either in vivo fitness distributions recorded beyond primary infection or in vitro distributions that are observed without adaptive immunity, suggesting the intrinsic viral fitness distribution may drive evolution. Simulated phylogenetic trees also agree with independent data and illuminate how phylogenetic inference must consider viral and immune-cell population dynamics to gain accurate mechanistic insights.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2109172119