P-A3 Limitations of CD32a expression as a marker of the HIV latent reservoir

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Abstract

It was recently reported that CD32a accurately marks CD4+ T cells from peripheral blood of ART suppressed people which harbor replication competent HIV. A direct marker of these latently infected cells may be expected to associate with reservoir size, but we find that expression levels of CD32 measured on CD4+ T cells isolated from the blood of 12 ART-suppressed participants did not correlate with measurements of cell-associated DNA or inducible virus in these individuals. We also examined genetic variation in CD32a, characterizing polymorphisms in 93 virally suppressed people on ART. Our analysis of all SNPs observed, including those reported to impact IgG binding and HIV disease progression, found no association of any CD32a variants with levels of HIV provirus. Given these results we attempted to repeat the primary cell sorting experiments described in the original report of CD32 as a marker of latently infected cells. CD4+ T cells with highest CD32 staining were sorted by flow cytometry from peripheral blood of ART suppressed people. These populations were not enriched in viral DNA compared to CD4+CD32- populations, in contrast to the original report. The lack of correlation we observe between variation in CD32 expression or genotype and reservoir size, and failure to replicate isolation of latent cells by sorting of CD4+ T cells based on CD32 staining, indicate CD32 may not be a direct marker of replication competent HIV in CD4+ T cell populations.

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