Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death
- Africa Health Research Institute, South Africa
- University of KwaZulu-Natal, South Africa
- University of Basel, Switzerland
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.
Article and author information
Author details
Funding
Human Frontier Science Program (CDA 00050/2013)
- Alex Sigal
European Research Council (Stg. 260686)
- Richard A Neher
DELTAS Africa Initiative (Graduate Fellowship)
- Isabella Markham Ferreira
National Research Foundation (Graduate Fellowship)
- Laurelle Jackson
National Institutes of Health (R21MH104220)
- Alex Sigal
National Research Foundation (Graduate Fellowship)
- Jessica Hunter
Poliomyelitis Research Foundation (Graduate Fellowship)
- Isabella Markham Ferreira
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Wenying Shou, Fred Hutchinson Cancer Research Center, United States
Ethics
Human subjects: Lymph nodes were obtained from the field of surgery of participants undergoing surgery for diagnostic purposes and/or complications of inflammatory lung disease. Informed consent was obtained from each participant, and the study protocol approved by the University of KwaZulu-Natal Institutional Review Board (approval BE024/09).
Version history
- Received: July 18, 2017
- Accepted: March 8, 2018
- Accepted Manuscript published: March 20, 2018 (version 1)
- Version of Record published: April 10, 2018 (version 2)
Copyright
© 2018, Jackson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death
eLife 7:e30134.
https://doi.org/10.7554/eLife.30134
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