Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death
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 on...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2018-03-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/30134 |
| _version_ | 1811253160941977600 |
|---|---|
| author | Laurelle Jackson Jessica Hunter Sandile Cele Isabella Markham Ferreira Andrew C Young Farina Karim Rajhmun Madansein Kaylesh J Dullabh Chih-Yuan Chen Noel J Buckels Yashica Ganga Khadija Khan Mikael Boulle Gila Lustig Richard A Neher Alex Sigal |
| author_facet | Laurelle Jackson Jessica Hunter Sandile Cele Isabella Markham Ferreira Andrew C Young Farina Karim Rajhmun Madansein Kaylesh J Dullabh Chih-Yuan Chen Noel J Buckels Yashica Ganga Khadija Khan Mikael Boulle Gila Lustig Richard A Neher Alex Sigal |
| author_sort | Laurelle Jackson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:46:39Z |
| format | Article |
| id | doaj.art-f962e22d605a430eaff5df1cc72a02f5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:46:39Z |
| publishDate | 2018-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f962e22d605a430eaff5df1cc72a02f52022-12-22T03:24:34ZengeLife Sciences Publications LtdeLife2050-084X2018-03-01710.7554/eLife.30134Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell deathLaurelle Jackson0Jessica Hunter1Sandile Cele2Isabella Markham Ferreira3Andrew C Young4https://orcid.org/0000-0003-3616-7956Farina Karim5Rajhmun Madansein6Kaylesh J Dullabh7Chih-Yuan Chen8Noel J Buckels9Yashica Ganga10Khadija Khan11Mikael Boulle12Gila Lustig13Richard A Neher14https://orcid.org/0000-0003-2525-1407Alex Sigal15https://orcid.org/0000-0001-8571-2004Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, Durban, South AfricaAfrica Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, Durban, South Africa; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, United StatesAfrica Health Research Institute, Durban, South AfricaDepartment of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South Africa; Centre for the AIDS Programme of Research in South Africa, Durban, South AfricaDepartment of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South AfricaDepartment of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South AfricaDepartment of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, Durban, South AfricaAfrica Health Research Institute, Durban, South AfricaAfrica Health Research Institute, Durban, South AfricaAfrica Health Research Institute, Durban, South AfricaBiozentrum, University of Basel, Basel, Switzerland; SIB Swiss Institute of Bioinformatics, Basel, SwitzerlandAfrica Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; Max Planck Institute for Infection Biology, Berlin, GermanyHIV 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.https://elifesciences.org/articles/30134HIV induced cell deathcell-to-cell spreadLymph nodeviral fitnessmultiple Infections per cell |
| spellingShingle | Laurelle Jackson Jessica Hunter Sandile Cele Isabella Markham Ferreira Andrew C Young Farina Karim Rajhmun Madansein Kaylesh J Dullabh Chih-Yuan Chen Noel J Buckels Yashica Ganga Khadija Khan Mikael Boulle Gila Lustig Richard A Neher Alex Sigal Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death eLife HIV induced cell death cell-to-cell spread Lymph node viral fitness multiple Infections per cell |
| title | Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death |
| title_full | Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death |
| title_fullStr | Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death |
| title_full_unstemmed | Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death |
| title_short | Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death |
| title_sort | incomplete inhibition of hiv infection results in more hiv infected lymph node cells by reducing cell death |
| topic | HIV induced cell death cell-to-cell spread Lymph node viral fitness multiple Infections per cell |
| url | https://elifesciences.org/articles/30134 |
| work_keys_str_mv | AT laurellejackson incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT jessicahunter incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT sandilecele incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT isabellamarkhamferreira incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT andrewcyoung incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT farinakarim incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT rajhmunmadansein incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT kayleshjdullabh incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT chihyuanchen incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT noeljbuckels incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT yashicaganga incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT khadijakhan incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT mikaelboulle incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT gilalustig incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT richardaneher incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath AT alexsigal incompleteinhibitionofhivinfectionresultsinmorehivinfectedlymphnodecellsbyreducingcelldeath |