| Autor: |
Mala K. Maini, Rajhmun Madansein, Ann-Kathrin Reuschl, Clemency Jolly, Dejan Mesner, John Thornhill, Alex Sigal, Kaylesh J. Dullabh, Laura J. Pallett, Shivkumar M, Sarah Fidler, Carolina Herrera, José Afonso Guerra-Assunção, Mahdad Noursadeghi |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.01.25.428084 |
| Popis: |
Human immunodeficiency virus type 1 (HIV-1) replicates in CD4+ T cells leading to profound T cell loss, immunological dysfunction and AIDS. Determining how HIV-1 shapes the immunological niche in which it resides to create a permissive environment is central to informing efforts to limit pathogenesis, disturb viral reservoirs and achieve a cure. A key roadblock in understanding HIV-T cell interactions is the requirement to activate CD4+ T cellsin vitroin order to make them permissive to infection. This dramatically alters T cell biology, obscuring native virus-host interactions. Here we show that HIV-1 cell-to-cell spread permits efficient and productive infection of resting CD4+ T cells without the need for prior activation. Infection is preferential for resting memory T cells, is observed with both CXCR4-tropic virus and CCR5-tropic transmitter-founder viruses and results in virus production and onward spreading infection. Strikingly, we find that HIV-1 infection of resting memory CD4+ T cells primes for induction of a tissue-resident memory (TRM)-like phenotype evidenced by upregulation of TRMmarkers CD69/CXCR6 alongside co-expression of CD49a, PD-1, CD101 as well as transcription factor Blimp-1. Furthermore, we reveal that HIV-1 initiates a transcriptional program that overlaps with the core TRMtranscriptional signature. This reprograming depends on the HIV-1 accessory protein Vpr. We propose that HIV-1 infection drives a CD4+ TRM-phenotype potentially sequestering infected cells within tissues to support viral replication and persistence. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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