Single-cell analysis of immune cell transcriptome during HIV-1 infection and therapy
Justin Pollara, Santosh Khanal, R. Whitney Edwards, Bhavna Hora, Guido Ferrari, Barton F. Haynes, Todd Bradley
Abstract
BACKGROUND: Cellular immune responses are phenotypically and functionally perturbed during HIV-1 infection, with the majority of function restored upon antiretroviral therapy (ART). Despite ART, residual inflammation remains that can lead to HIV-related co-morbidities and mortality, indicating that ART does not fully restore normal immune cell function. Thus, understanding the dynamics of the immune cell landscape during HIV-1 infection and ART is critical to defining cellular dysfunction that occurs during HIV-1 infection and imprints during therapy. RESULTS: Here, we have applied single-cell transcriptome sequencing of peripheral blood immune cells from chronic untreated HIV-1 individuals, HIV-1-infected individuals receiving ART and HIV-1 negative individuals. We also applied single-cell transcriptome sequencing to a primary cell model of early HIV-1 infection using CD4+ T cells from healthy donors. We described changes in the transcriptome at high resolution that occurred during HIV-1 infection, and perturbations that remained during ART. We also determined transcriptional differences among T cells expressing HIV-1 transcripts that identified key regulators of HIV-1 infection that may serve as targets for future therapies to block HIV-1 infection. CONCLUSIONS: This work identified key molecular pathways that are altered in immune cells during chronic HIV-1 infection that could remain despite therapy. We also identified key genes that are upregulated during early HIV-1 infection that provide insights on the mechanism of HIV-1 infection and could be targets for future therapy.