Principles Governing Establishment versus Collapse of HIV-1 Cellular Spread

Cell Host Microbe. 2019 Dec 11;26(6):748-763.e20. doi: 10.1016/j.chom.2019.10.006. Epub 2019 Nov 21.


A population at low census might go extinct or instead transition into exponential growth to become firmly established. Whether this pivotal event occurs for a within-host pathogen can be the difference between health and illness. Here, we define the principles governing whether HIV-1 spread among cells fails or becomes established by coupling stochastic modeling with laboratory experiments. Following ex vivo activation of latently infected CD4 T cells without de novo infection, stochastic cell division and death contributes to high variability in the magnitude of initial virus release. Transition to exponential HIV-1 spread often fails due to release of an insufficient amount of replication-competent virus. Establishment of exponential growth occurs when virus produced from multiple infected cells exceeds a critical population size. We quantitatively define the crucial transition to exponential viral spread. Thwarting this process would prevent HIV transmission or rebound from the latent reservoir.

Keywords: Allee effect; HIV; critical threshold; exponential growth; latency; latent reservoir; mathematical modeling; population dynamics; rebound; viral dynamics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • CD4-Positive T-Lymphocytes / virology
  • HIV Infections / epidemiology*
  • HIV Infections / transmission
  • HIV-1* / growth & development
  • HIV-1* / metabolism
  • Humans
  • Models, Biological
  • Population Dynamics / statistics & numerical data
  • Viral Load
  • Virus Activation
  • Virus Latency
  • Virus Replication

Associated data

  • Dryad/10.5061/dryad.wdbrv15j3