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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 Young, Farina Karim, Rajhmun Madansein, Kaylesh J. Dullabh, Chih-Yuan Chen, Noel J. Buckels, Yashica Ganga, Khadija Khan, Mikaël Boullé, Gila Lustig, View ORCID ProfileRichard A. Neher, View ORCID ProfileAlex Sigal
doi: https://doi.org/10.1101/163352
Laurelle Jackson
1Africa Health Research Institute, Durban, South Africa.
2School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
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Jessica Hunter
1Africa Health Research Institute, Durban, South Africa.
2School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
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Sandile Cele
1Africa Health Research Institute, Durban, South Africa.
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Isabella Markham Ferreira
1Africa Health Research Institute, Durban, South Africa.
2School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
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Andrew Young
1Africa Health Research Institute, Durban, South Africa.
3Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
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Farina Karim
1Africa Health Research Institute, Durban, South Africa.
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Rajhmun Madansein
4Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South Africa.
5Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
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Kaylesh J. Dullabh
4Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South Africa.
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Chih-Yuan Chen
4Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South Africa.
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Noel J. Buckels
4Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South Africa.
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Yashica Ganga
1Africa Health Research Institute, Durban, South Africa.
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Khadija Khan
1Africa Health Research Institute, Durban, South Africa.
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Mikaël Boullé
1Africa Health Research Institute, Durban, South Africa.
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Gila Lustig
1Africa Health Research Institute, Durban, South Africa.
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Richard A. Neher
6Biozentrum, University of Basel, Switzerland.
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Alex Sigal
1Africa Health Research Institute, Durban, South Africa.
2School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
7Max Planck Institute for Infection Biology, Berlin, Germany.
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  • For correspondence: alex.sigal@k-rith.org sigal@mpiib-berlin.mpg.de
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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 transmission which involves 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, as 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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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 13, 2017.
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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 Young, Farina Karim, Rajhmun Madansein, Kaylesh J. Dullabh, Chih-Yuan Chen, Noel J. Buckels, Yashica Ganga, Khadija Khan, Mikaël Boullé, Gila Lustig, Richard A. Neher, Alex Sigal
bioRxiv 163352; doi: https://doi.org/10.1101/163352
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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 Young, Farina Karim, Rajhmun Madansein, Kaylesh J. Dullabh, Chih-Yuan Chen, Noel J. Buckels, Yashica Ganga, Khadija Khan, Mikaël Boullé, Gila Lustig, Richard A. Neher, Alex Sigal
bioRxiv 163352; doi: https://doi.org/10.1101/163352

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