Abstract
The spikes on virus surfaces bind receptors on host cells to propagate infection. High spike densities (SDs) can promote infection, but spikes are also targets of antibody-mediated immune responses. Thus, diverse evolutionary pressures can influence virus SDs. HIV's SD is about two orders of magnitude lower than that of other viruses, a surprising feature of unknown origin. By modeling antibody evolution through affinity maturation, we find that an intermediate SD maximizes the affinity of generated antibodies. We argue that this leads most viruses to evolve high SDs. T helper cells, which are depleted during early HIV infection, play a key role in antibody evolution. We find that T helper cell depletion results in high affinity antibodies when SD is high, but not if SD is low. This special feature of HIV infection may have led to the evolution of a low SD to avoid potent immune responses early in infection.
Original language | English |
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Article number | e1006408 |
Journal | PLoS Computational Biology |
Volume | 14 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2018 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2018 Amitai 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.
Funding
Financial support for this work was provided by a grant from the Ragon Institute of MGH, MIT, & Harvard (AKC, AA). MK acknowledges support from NSF grant no. DMR-1708280. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funders | Funder number |
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AKC | |
National Science Foundation | DMR-1708280 |
Directorate for Mathematical and Physical Sciences | 1708280 |
Ragon Institute of MGH, MIT and Harvard |