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Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo

Horwitz JA, et al., 170(4):637-648.e10, Cell, 2017

The glycoprotein spikes located on the surface of HIV-1 virus are composed of two non-covalently associated subunits, gp41 and gp120. HIV virion uses gp120 to attach itself to CD4 receptors on the host cells. Most of the individuals infected by HIV-1 develop non-neutralizing antibodies (nnAbs) during initial stages of the infection. Described herein are the effects of nnAbs on the course of HIV-1 infection in vivo. Authors have engineered a recombinant HIV-1 reporter virus that expresses a heterologous hemagglutinin-tag (HA-tag) on the surface of infected cells and virions. Binding kinetics of soluble 2-domain CD4 (2dCD4) binding to the YU2.SOSIP.664 constructs were studied by using Bio-Layer Interferometry (BLI). A Pall ForteBio Octet QKe system equipped with Ni-NTA (NTA) biosensors was used to perform all BLI assays. NTA sensor tips were loaded with HIS-tagged 2dCD4 until saturation. Association and dissociation kinetics were assessed by dipping the loaded NTA sensor tips in a concentration series of SOSIP.664 trimer samples. BLI data analyses were executed using nonlinear regression curve fitting using the Graphpad Prism software. Equilibrium dissociation constants (KD values) for the binding interactions were determined. Overall results of this study suggest that nnAbs can protect against and alter the course of HIV-1 infection by applying immune pressure on the infecting virus.

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