Format

Send to

Choose Destination
Cell Rep. 2018 Dec 26;25(13):3844-3857.e5. doi: 10.1016/j.celrep.2018.12.009.

Cell Size-Based Decision-Making of a Viral Gene Circuit.

Author information

1
Department of Bioengineering, University of Illinois at Urbana-Champaign, 321 Everitt Laboratory, 1406 West Green Street, Urbana, IL 61801, USA.
2
Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, 1110 West Green Street, Urbana, IL 61801, USA.
3
Department of Bioengineering, University of Illinois at Urbana-Champaign, 321 Everitt Laboratory, 1406 West Green Street, Urbana, IL 61801, USA; Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, 306 North Wright St, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, 1110 West Green Street, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 West Gregory Drive, Urbana, IL 61801, USA. Electronic address: roydar@illinois.edu.

Abstract

Latently infected T cells able to reinitiate viral propagation throughout the body remain a major barrier to curing HIV. Distinguishing between latently infected cells and uninfected cells will advance efforts for viral eradication. HIV decision-making between latency and active replication is stochastic, and drug cocktails that increase bursts of viral gene expression enhance reactivation from latency. Here, we show that a larger host-cell size provides a natural cellular mechanism for enhancing burst size of viral expression and is necessary to destabilize the latent state and bias viral decision-making. Latently infected Jurkat and primary CD4+ T cells reactivate exclusively in larger activated cells, while smaller cells remain silent. In addition, reactivation is cell-cycle dependent and can be modulated with cell-cycle-arresting compounds. Cell size and cell-cycle dependent decision-making of viral circuits may guide stochastic design strategies and applications in synthetic biology and may provide important determinants to advance diagnostics and therapies.

PMID:
30590053
DOI:
10.1016/j.celrep.2018.12.009
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center