Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
X
Announcing the new Tapestri scMRD Assay for AML. Learn More
X
publication

Phenotypic signatures of immune selection in HIV-1 reservoir cells


Weiwei Sun et al.
Nature
Abstract

Human immunodeficiency virus 1 (HIV-1) reservoir cells persist lifelong despite antiretroviral treatment1,2 but may be vulnerable to host immune responses that could be exploited in strategies to cure HIV-1. Here we used a single-cell, next-generation sequencing approach for the direct ex vivo phenotypic profiling of individual HIV-1-infected memory CD4+ T cells from peripheral blood and lymph nodes of people living with HIV-1 and receiving antiretroviral treatment for approximately 10 years. We demonstrate that in peripheral blood, cells harbouring genome-intact proviruses and large clones of virally infected cells frequently express ensemble signatures of surface markers conferring increased resistance to immune-mediated killing by cytotoxic T and natural killer cells, paired with elevated levels of expression of immune checkpoint markers likely to limit proviral gene transcription; this phenotypic profile might reduce HIV-1 reservoir cell exposure to and killing by cellular host immune responses. Viral reservoir cells harbouring intact HIV-1 from lymph nodes exhibited a phenotypic signature primarily characterized by upregulation of surface markers promoting cell survival, including CD44, CD28, CD127 and the IL-21 receptor. Together, these results suggest compartmentalized phenotypic signatures of immune selection in HIV-1 reservoir cells, implying that only small subsets of infected cells with optimal adaptation to their anatomical immune microenvironment are able to survive during long-term antiretroviral treatment. The identification of phenotypic markers distinguishing viral reservoir cells may inform future approaches for strategies to cure and eradicate HIV-1.



Authors

Weiwei Sun



VIEW

publication
Mutated cells mediate distinct inflammatory responses in clonal hematopoiesis
J. Brett Heimlich
BioRxiv
publication
scTAM-seq enables targeted high-confidence analysis of DNA methylation in single cells
Bianchi A
Genome Biology (2022)
publication
Single cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia
Troy T. Robinson
BioRxiv (2022)
publication
The genomic landscape of pediatric acute lymphoblastic leukemia
Samuel W. Brady
Nature Genetics
REQUEST QUOTE