Effect of Synaptic Transmission on Viral Fitness in HIV Infection

Natalia L. Komarova, David Levy, Dominik Wodarz

Research output: Contribution to journalArticle

Abstract

HIV can spread through its target cell population either via cell-free transmission, or by cell-to-cell transmission, presumably through virological synapses. Synaptic transmission entails the transfer of tens to hundreds of viruses per synapse, a fraction of which successfully integrate into the target cell genome. It is currently not understood how synaptic transmission affects viral fitness. Using a mathematical model, we investigate how different synaptic transmission strategies, defined by the number of viruses passed per synapse, influence the basic reproductive ratio of the virus, R0, and virus load. In the most basic scenario, the model suggests that R0 is maximized if a single virus particle is transferred per synapse. R0 decreases and the infection eventually cannot be maintained for larger numbers of transferred viruses, because multiple infection of the same cell wastes viruses that could otherwise enter uninfected cells. To explain the relatively large number of HIV copies transferred per synapse, we consider additional biological assumptions under which an intermediate number of viruses transferred per synapse could maximize R0. These include an increased burst size in multiply infected cells, the saturation of anti-viral factors upon infection of cells, and rate limiting steps during the process of synapse formation.

Original languageEnglish (US)
Article numbere48361
JournalPLoS One
Volume7
Issue number11
DOIs
StatePublished - Nov 15 2012

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synaptic transmission
HIV infections
Viruses
Synaptic Transmission
HIV Infections
synapse
Synapses
viruses
cells
Cells
Infection
HIV
infection
Health Services Needs and Demand
viral load
virion
Virion
Genes
Theoretical Models
mathematical models

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Effect of Synaptic Transmission on Viral Fitness in HIV Infection. / Komarova, Natalia L.; Levy, David; Wodarz, Dominik.

In: PLoS One, Vol. 7, No. 11, e48361, 15.11.2012.

Research output: Contribution to journalArticle

Komarova, Natalia L. ; Levy, David ; Wodarz, Dominik. / Effect of Synaptic Transmission on Viral Fitness in HIV Infection. In: PLoS One. 2012 ; Vol. 7, No. 11.
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