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Nat Commun. 2020 Jan 9;11(1):147. doi: 10.1038/s41467-019-13837-4.

Sensing of HIV-1 by TLR8 activates human T cells and reverses latency.

Author information

1
Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
2
Department of Infectious Diseases, St. Olavs Hospital, Trondheim, Norway.
3
School of Pharmaceutical Sciences, Tsinghua University-Peking University Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, 100082, Beijing, China.
4
Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway.
5
Department of Medical Microbiology, St. Olavs Hospital, Trondheim, Norway.
6
Department of Cancer Immunology, Institute of Cancer Research, Oslo University Hospital, Oslo, Norway.
7
K.G. Jebsen Centre for Cancer Immunotherapy, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
8
Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. trude.flo@ntnu.no.
9
Department of Infectious Diseases, St. Olavs Hospital, Trondheim, Norway. trude.flo@ntnu.no.
10
Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway. trude.flo@ntnu.no.

Abstract

During HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well understood. Here we show that synthetic ligands of TLR8 boosted T cell receptor signaling, resulting in increased cytokine production and upregulation of surface activation markers. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation towards Th1 and Th17. In addition, we found that endosomal HIV induced cytokine secretion from CD4+ T cells in a TLR8-specific manner. TLR8 engagement also enhanced HIV-1 replication and potentiated the reversal of latency in patient-derived T cells. The adjuvant TLR8 activity in T cells can contribute to viral dissemination in the lymph node and low-grade inflammation in HIV patients. In addition, it can potentially be exploited for therapeutic targeting and vaccine development.

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