Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death
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Hunter, Jessica
Cele, Sandile
Ferreira, Isabella Markham
Young, Andrew C
Karim, Farina
Madansein, Rajhmun
Dullabh, Kaylesh J
Chen, Chih-Yuan
Buckels, Noel J
Ganga, Yashica
Khan, Khadija
Boulle, Mikael
Lustig, Gila
Neher, Richard A
et al.
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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.
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eLife
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7
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© 2018, Jackson et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Biological sciences
Biomedical and clinical sciences
Health sciences
HIV induced cell death
Lymph node
cell-to-cell spread
computational biology
human
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Jackson, L; Hunter, J; Cele, S; Ferreira, IM; Young, AC; Karim, F; Madansein, R; Dullabh, KJ; Chen, C-Y; Buckels, NJ; Ganga, Y; Khan, K; Boulle, M; Lustig, G; Neher, RA; et al., Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death, eLife, 2018, 7, pp. e30134