Journal Article

Single-cell analysis of immune cell transcriptome during HIV-1 infection and therapy

Pollara, Justin, Ferrari, Guido, Edwards, R. Whitney, Hora, Bhavna, Haynes, Barton F., Bradley, Todd, Khanal, Santosh

2022

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acquired immune deficiency syndrome / AIDS / Allergology / Analysis / Antiretroviral drugs / Antiretroviral therapy / Biomedical and Life Sciences / Biomedicine / Care and treatment / CD4 antigen / CD4-Positive T-Lymphocytes / Chronic infection / Cytokines and Growth Factors / Diagnosis / Gene expression / Genomics / Graft vs Host Disease / Health aspects / HIV / HIV infection / HIV Infections - drug therapy / HIV-1 / HIV-1 infection / Human immunodeficiency virus / Humans / Immune cells / Immune response / Immune response (cell-mediated) / Immune system / Immunology / Infections / Lymphocytes / Lymphocytes T / Peripheral blood / Recovery of function / RNA sequencing / Single-Cell Analysis / Single-cell RNA-seq / Transcription factors / Transcriptome / Transcriptomes / Vaccine