Generation and characterization of iPSC models from HIV-1-positive individuals with divergent clinical outcomes

TL;DR

Researchers created 50 HIV-free stem cell lines from HIV-positive individuals with different disease outcomes to study how host genetics influence HIV progression.

Contribution

The novel contribution is generating a diverse, HIV-1-free iPSC resource from HIV-positive individuals with known clinical outcomes for mechanistic studies.

Findings

iPSC lines are HIV-1 negative, pluripotent, and can differentiate into HIV-1 target macrophages.

Derived macrophages support productive HIV-1 infection and lentiviral vector transduction.

The resource enables in vitro modeling of host determinants of HIV-1 pathogenesis.

Abstract

The clinical outcome of human immunodeficiency virus type-1 (HIV-1) infection varies greatly among individuals, ranging from rapid disease progression to natural viral suppression. While viral and environmental factors contribute, host genetics are considered major determinants of disease trajectory. To enable mechanistic studies of host factors underlying disease outcomes, we generated 50 induced pluripotent stem cell (iPSC) lines from 18 participants of the Multicenter AIDS Cohort Study (MACS), spanning a spectrum of clinical trajectories. Reprogrammed MACS lines are confirmed to be HIV-1 negative and Sendai vector-free. We validate their pluripotency and demonstrate robust differentiation into macrophages capable of productive HIV-1 infection. These MACS-iPSC lines offer a genetically diverse resource to model HIV-1 infection in vitro, where clinical progression is known. Crucially, their capacity to differentiate into HIV-1 target cells and other disease-relevant lineages makes them a powerful tool to uncover host determinants of HIV-1 pathogenesis and advance targeted treatment and curative strategies.

•50 new iPSC lines from 18 HIV-1-positive donors with diverse clinical histories•Reprogrammed iPSC lines are HIV-1-free and pluripotent•These iPSCs can be differentiated into macrophages, a natural HIV-1 target cell•This resource supports lentiviral vector transduction and replicating HIV-1 studies

50 new iPSC lines from 18 HIV-1-positive donors with diverse clinical histories

Reprogrammed iPSC lines are HIV-1-free and pluripotent

These iPSCs can be differentiated into macrophages, a natural HIV-1 target cell

This resource supports lentiviral vector transduction and replicating HIV-1 studies

We generated 50 HIV-1-free iPSC lines from 18 long-term cryopreserved blood samples from HIV-1-positive patients with diverse clinical histories. These iPSCs can be differentiated into macrophages, an HIV-1 cell target. Both cell types can be infected with lentiviral vectors, and derived macrophages are permissive to replicating HIV-1. This sharable resource enables HIV-1 host susceptibility studies and research on other pathogens.

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