The low spike density of HIV may have evolved because of the effects of T helper cell depletion on affinity maturation

Assaf Amitai, Arup K. Chakraborty, Mehran Kardar

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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 languageEnglish
Article numbere1006408
JournalPLoS Computational Biology
Volume14
Issue number8
DOIs
StatePublished - Aug 2018
Externally publishedYes

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.

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