DOI: 10.5061/dryad.wdbrv15j3
title: Principles Governing Establishment versus Collapse of HIV-1 Cellular Spread

description: 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.
description: The file "code-data-HatayeJ.zip" contains two
 experimental data tables and script code in R, details are in the file
 "README.txt". These files were generated for
 this research publication: Principles Governing
 Establishment versus Collapse of HIV-1 Cellular Spread
 Hataye JM et al. Cell Host & Microbe, 2019 
 https://doi.org/10.1016/j.chom.2019.10.006 See this publication for details. It has an extensive methods section. The HIV env sequencing for this study was deposited at Genbank (https://www.ncbi.nlm.nih.gov/genbank/) with accession numbers MN515491-MN516420. There are two experimental data files in the directory /expData HIVrna1.txt, HIV RNA detection data (RT-PCR) from ex vivo culture supernatants using CD4+ T cells isolated from the peripheral blood of human donors with HIV-1 infection on combination antiretroviral therapy (ART). These data are organized into a table with columns with the following headings: well: culture well index  set: experiment set index pid: patient ID (anonymized) cd4: clinical CD4+ T cell count on day of donation vl: clinical HIV viral load on day of donation outg: If TRUE then cultures had exogenous target cells plus IL-2 added for outgrowth conditions efv: If TRUE then cultures had efavirenz (reverse-transcriptase inhibitor) added for viral inhibition conditions tcab: If TRUE then cultures had T cell activation beads (containing anti-CD3, anti-CD2, anti-CD28) added days: days of culture cells: number of CD4+ T cells added to culture on day 0 (day of sorting) rcas: fraction of RCAS retroviral RNA recovered (range 0-1). dna: HIV DNA copies detected from entire culture supernatant following DNAse treatment rna: HIV RNA copies in entire culture supernatant (based on gag RT-PCR reaction, dilution factors and RCAS recovery) rnac: HIV RNA copies in entire culture supernatant, corrected for residual HIV DNA if present   HIVrna2.txt, HIV RNA detection data (RT-PCR) from secondary (virus transfer from primary culture) and tertiary HIV culture supernatants. The remaining directories contain simulation results or R code to perform data analysis, plotting, fitting of ordinary differential equation models, stochastic simulation, and Bayesian inference in Stan.
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