Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death

Laurelle Jackson, Jessica Hunter, Sandile Cele, Isabella Markham Ferreira, Andrew C. Young, Farina Karim, Rajhmun Madansein, Kaylesh J. Dullabh, Chih-Yuan Chen, Noel J. Buckels, Yashica Ganga, Khadija Khan, Mikael Boulle, Gila Lustig, Richard A. Neher, Alex Sigal

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
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Abstract

HIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmissions of multiple virions per cell could lead to increased numbers of live infected cells. If the number of viral DNA copies remains above one after inhibition, then eliminating the surplus viral copies reduces cell death. Using a cell line, we observed increased numbers of live infected cells when infection was partially inhibited with the antiretroviral efavirenz or neutralizing antibody. We then used efavirenz at concentrations reported in lymph nodes to inhibit lymph node infection by partially resistant HIV mutants. We observed more live infected lymph node cells, but with fewer HIV DNA copies per cell, relative to no drug. Hence, counterintuitively, limited attenuation of HIV transmission per cell may increase live infected cell numbers in environments where the force of infection is high.

Original languageEnglish
Article numbere30134
Number of pages24
JournaleLife
Volume7
DOIs
Publication statusPublished - 20 Mar 2018
Externally publishedYes

Keywords

  • cell-to-cell spread
  • computational and systems biology
  • HIV induced cell death
  • lymph node
  • multiple infections per cell
  • viral fitness

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