AI Article Synopsis

  • * The study introduces two single-chain diabodies (scDbs) that specifically target the HIV-1 envelope protein and enhance the activity of natural killer (NK) cells, which are crucial for fighting infections.
  • * Experiments show that these scDbs can significantly reduce the number of reservoir cells in vitro and in animal models, suggesting they could be promising candidates for future HIV-1 treatments.

Article Abstract

The persistence of CD4 T cells carrying latent human immunodeficiency virus-1 (HIV-1) proviruses is the main barrier to a cure. New therapeutics to enhance HIV-1-specific immune responses and clear infected cells will probably be necessary to achieve reduction of the latent reservoir. In the present study, we report two single-chain diabodies (scDbs) that target the HIV-1 envelope protein (Env) and the human type III Fcγ receptor (CD16). We show that the scDbs promoted robust and HIV-1-specific natural killer (NK) cell activation and NK cell-mediated lysis of infected cells. Cocultures of CD4 T cells from people with HIV-1 on antiretroviral therapy (ART) with autologous NK cells and the scDbs resulted in marked elimination of reservoir cells that was dependent on latency reversal. Treatment of human interleukin-15 transgenic NSG mice with one of the scDbs after ART initiation enhanced NK cell activity and reduced reservoir size. Thus, HIV-1-specific scDbs merit further evaluation as potential therapeutics for clearance of the latent reservoir.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907297PMC
http://dx.doi.org/10.1038/s41590-023-01741-5DOI Listing

Publication Analysis

Top Keywords

natural killer
8
reservoir cells
8
cd4 cells
8
infected cells
8
latent reservoir
8
cells
7
reservoir
5
scdbs
5
bispecific antibodies
4
antibodies promote
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!