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Cell. 2014 Aug 28;158(5):989-99. doi: 10.1016/j.cell.2014.07.043. Epub 2014 Aug 14.

Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice.

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
2
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA.
3
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USA.
4
Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, NY 10065, USA.
5
Epinova DPU, Immuno-Inflammation Therapy Area, Medicines Research Centre, GlaxoSmithKline, Stevenage SG1 2NY, UK.
6
Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
7
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute. Electronic address: nussen@rockefeller.edu.

Abstract

Latent reservoirs of HIV-1-infected cells are refractory to antiretroviral therapies (ART) and remain the major barrier to curing HIV-1. Because latently infected cells are long-lived, immunologically invisible, and may undergo homeostatic proliferation, a "shock and kill" approach has been proposed to eradicate this reservoir by combining ART with inducers of viral transcription. However, all attempts to alter the HIV-1 reservoir in vivo have failed to date. Using humanized mice, we show that broadly neutralizing antibodies (bNAbs) can interfere with establishment of a silent reservoir by Fc-FcR-mediated mechanisms. In established infection, bNAbs or bNAbs plus single inducers are ineffective in preventing viral rebound. However, bNAbs plus a combination of inducers that act by independent mechanisms synergize to decrease the reservoir as measured by viral rebound. Thus, combinations of inducers and bNAbs constitute a therapeutic strategy that impacts the establishment and maintenance of the HIV-1 reservoir in humanized mice.

Comment in

PMID:
25131989
PMCID:
PMC4163911
DOI:
10.1016/j.cell.2014.07.043
[Indexed for MEDLINE]
Free PMC Article
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