Phenotypic signatures of immune selection in HIV-1 reservoir cells

作者：Weiwei Sun, Ce Gao, Ciputra Adijaya Hartana, Matthew R. Osborn, Kevin Einkauf, Xiaodong Lian, Benjamin Bone, Nathalie Bonheur, Tae‐Wook Chun, Eric Rosenberg, Bruce D. Walker, Xu G. Yu, Mathias Lichterfeld · 发表于：Nature · 年份：2023 · DOI：10.1038/s41586-022-05538-8 · 被引用次数：195 · 研究领域：HIV Research and Treatment、Immune Cell Function and Interaction、T-cell and B-cell Immunology

Abstract Human immunodeficiency virus 1 (HIV-1) reservoir cells persist lifelong despite antiretroviral treatment 1,2 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 a...