Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death
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Author
Jackson, Laurelle
Hunter, Jessica
Cele, Sandile
Ferreira, Isabella Markham
Karim, Farina
Madansein, Rajhmun
Dullabh, Kaylesh J
Chen, Chih-Yuan
Buckels, Noel J
Ganga, Yashica
Khan, Khadija
Boulle, Mikael
Lustig, Gila
Neher, Richard A
Sigal, Alex
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.7554/eLife.30134Metadata
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Jackson, L., J. Hunter, S. Cele, I. M. Ferreira, A. C. Young, F. Karim, R. Madansein, et al. 2018. “Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death.” eLife 7 (1): e30134. doi:10.7554/eLife.30134. http://dx.doi.org/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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896883/pdf/Terms of Use
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