RT Journal Article
SR Electronic
T1 Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 163352
DO 10.1101/163352
A1 Laurelle Jackson
A1 Jessica Hunter
A1 Sandile Cele
A1 Isabella Markham Ferreira
A1 Andrew Young
A1 Farina Karim
A1 Rajhmun Madansein
A1 Kaylesh J. Dullabh
A1 Chih-Yuan Chen
A1 Noel J. Buckels
A1 Yashica Ganga
A1 Khadija Khan
A1 Mikaël Boullé
A1 Gila Lustig
A1 Richard A. Neher
A1 Alex Sigal
YR 2017
UL http://biorxiv.org/content/early/2017/07/13/163352.abstract
AB 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.