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

Jackson, Laurelle and Hunter, Jessica and Cele, Sandile and Ferreira, Isabella Markham and Young, Andrew C. and Karim, Farina and Madansein, Rajhmun and Dullabh, Kaylesh J. and Chen, Chih-Yuan and Buckels, Noel J. and Ganga, Yashica and Khan, Khadija and Boulle, Mikael and Lustig, Gila and Neher, Richard A. and Sigal, Alex. (2018) Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death. eLife, 7 (e30134). pp. 1-24.

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Official URL: https://edoc.unibas.ch/65360/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Computational Modeling of Biological Processes (Neher)
UniBasel Contributors:Neher, Richard A
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:eLife Sciences Publications
ISSN:2050-084X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Nov 2019 14:53
Deposited On:12 Sep 2019 14:45

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