Journal Article

DZNE-2026-00233

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Persistent viral control status is associated with enhanced innate immune responses in people with HIV-1

C. dos Santos, J. ; Groenendijk, A. L. ; Ruijten, S. D. E. ; Knoll, R.DZNE* ; Vadaq, N. ; Horst, R. t. ; Fok, E. T. ; Witkowski, W. ; Blaauw, M. J. T. ; van Eekeren, L. E. ; Vos, W. A. J. W. ; Cleophas-Jacobs, M. ; Reichl, S. ; Otten, T. ; Martens, J. H. A. ; van der Meer, A. ; Koninkx, H. ; de Jonge, M. I. ; Beyer, M. D.DZNE* ; van Lunzen, J. ; Joosten, L. A. B. ; Bock, C. ; Rokx, C. ; Verbon, A. ; Vandekerckhove, L. ; Aschenbrenner, A. C.DZNE* ; Schultze, J. L.DZNE* ; Matzaraki, V. ; van der Ven, A. J. A. M. ; Netea, M. G.

2026
Elsevier St. Louis

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Please use a persistent id in citations: doi:10.1016/j.isci.2026.114807

Abstract: The mechanisms mediating elite and persistent HIV control in people living with HIV (PLHIV) are only partially understood and largely attributed to adaptive T cell responses, but whether innate immunity also contributes remains unclear. Using samples from the 2000HIV study, we examined the transcriptional and functional profiles of monocytes from spontaneous HIV controllers and normal progressors on long-term antiretroviral therapy. HIV controllers displayed enhanced cytokine production after bacterial and viral stimulation, alongside antiviral and interferon-inducible transcriptional signatures and reduced inflammatory gene expression. Persistent controllers further showed increased capacity for trained immunity, with H3K4me3 profiling indicating the epigenetic priming of innate immune genes. Remarkably, relatives of persistent controllers also exhibited stronger innate and trained immune responses than relatives of normal progressors. These findings suggest that robust innate immunity, particularly monocyte function, may precede infection and contribute to sustained HIV control, offering new avenues for therapies that induce similar innate antiviral responses.

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Contributing Institute(s):

1. Aging and Immunity (AG Aschenbrenner)
2. Immunogenomics and Neurodegeneration (AG Beyer)
3. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)
4. Platform for Single Cell Genomics and Epigenomics (PRECISE)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)
2. 351 - Brain Function (POF4-351) (POF4-351)
3. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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