Principles Governing Establishment versus Collapse of HIV-1 Cellular Spread

Author:

Hataye, Jason M

Casazza, Joseph P

Best, Katharine

Liang, C Jason

Immonen,Taina

Ambrozak, David R

Darko, Samuel

Henry, Amy R

Laboune, Farida

Maldarelli,Frank

Douek, Daniel C

Hengartner, Nicolas W

Yamamoto, Takuya

Keele,Brandon

Perelson, Alan S

Koup, Richard A
Author Address

Immunology Section, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. Electronic address: jason.hataye@nih.gov., Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA., Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Rockville, MD 20892, USA., AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., Human Immunology Section, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA., HIV Dynamics and Replication Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., Laboratory of Immunosenescence, National Institutes of Biomedical Innovation, Health, and Nutrition, Osaka 567-0085, Japan., Immunology Section, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. Electronic address: rkoup@mail.nih.gov.,

Abstract:

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. Published by Elsevier Inc.

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