1. Computational and Systems Biology
  2. Microbiology and Infectious Disease
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Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death

  1. Laurelle Jackson
  2. Jessica Hunter
  3. Sandile Cele
  4. Isabella Markham Ferreira
  5. Andrew C Young
  6. Farina Karim
  7. Rajhmun Madansein
  8. Kaylesh J Dullabh
  9. Chih-Yuan Chen
  10. Noel J Buckels
  11. Yashica Ganga
  12. Khadija Khan
  13. Mikael Boulle
  14. Gila Lustig
  15. Richard A Neher
  16. Alex Sigal  Is a corresponding author
  1. Africa Health Research Institute, South Africa
  2. University of KwaZulu-Natal, South Africa
  3. University of Basel, Switzerland
Research Article
  • Cited 2
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Cite this article as: eLife 2018;7:e30134 doi: 10.7554/eLife.30134

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

  1. Laurelle Jackson

    Systems Infection Biology, Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  2. Jessica Hunter

    Systems Infection Biology, Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  3. Sandile Cele

    Systems Infection Biology, Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  4. Isabella Markham Ferreira

    Systems Infection Biology, Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  5. Andrew C Young

    Systems Infection Biology, Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3616-7956
  6. Farina Karim

    Division of Clinical Studies, Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  7. Rajhmun Madansein

    Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    No competing interests declared.
  8. Kaylesh J Dullabh

    Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    No competing interests declared.
  9. Chih-Yuan Chen

    Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    No competing interests declared.
  10. Noel J Buckels

    Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    No competing interests declared.
  11. Yashica Ganga

    Division of Clinical Studies, Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  12. Khadija Khan

    Division of Clinical Studies, Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  13. Mikael Boulle

    Division of Clinical Studies, Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  14. Gila Lustig

    Division of Clinical Studies, Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  15. Richard A Neher

    Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    Richard A Neher, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2525-1407
  16. Alex Sigal

    Systems Infection Biology, Africa Health Research Institute, Durban, South Africa
    For correspondence
    alex.sigal@k-rith.org
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8571-2004

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.

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).

Reviewing Editor

  1. Wenying Shou, Fred Hutchinson Cancer Research Center, United States

Publication history

  1. Received: July 18, 2017
  2. Accepted: March 8, 2018
  3. Accepted Manuscript published: March 20, 2018 (version 1)
  4. 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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