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4th Edition of World Congress on Infectious Diseases

June 21-22, 2023 | Rome, Italy

June 21 -22, 2023 | Rome, Italy
Infection 2023

Hertel Quentin

Speaker at World Congress on Infectious Diseases 2023 - Hertel Quentin
University of Montpellier, France
Title : Calcium-dependent restriction of HIV-1 by S100A9 in myeloid cells

Abstract:

The alarmin S100A9 is a calcium-binding protein known for its pro-inflammatory extracellular role in the immune response against pathogens in the form of a S100A8/S100A9 heterodimer called calprotectin. However, S100A9 was recently shown to exert an intracellular antiviral effect against HIV-1 infection of Langherans cells, a cutaneous- and mucosal-resident subset of dendritic cells. The calcium-dependent ability of S100A9 and calprotectin to bind various divalent cations is required for its known pro-inflammatory and antibacterial roles, and previous in vitro experiments point towards a role of S100A9-dependent magnesium chelation in HIV-1 reverse transcriptase (RT) inhibition. Our project aims to better characterize the role of calcium in S100A9-mediated HIV-1 restriction in immune myeloid cell subsets. Using a homemade S100A9 CRISPR-knockout THP-1 cellular model, we generated myeloid THP-1 cell lines stably expressing wild-type and calcium-binding deficient mutants of S100A9. Our results show that cells expressing calcium-binding mutants exhibit no antiviral effect against HIV-GFP pseudotyped lentivectors or wild-type HIV-1 infection compared to S100A9-WT expressing THP-1 cells. Additionally, the observed inhibition of HIV-RT enzymatic activity in-vitro by S100A9-WT protein is lost upon targeted calcium-binding site mutations. Finally, pharmacological increase of intracellular calcium stores into the cytosol with ionomycin shortly after virus entry overcomes S100A9-WT antiviral effect while having no effect on calcium-binding deficient mutants or when treatment is applied at later stages of the viral replication cycle. Together, these results suggest a calcium-dependent antiviral effect of alarmin S100A9 against HIV-1 in a human myeloid cell model.

Audience take away: 

  • These results characterize a new intracellular mechanism for the alarmin S100A9, highly expressed in myeloid cells, expanding the scope of its known functions beyond the well-described extracellular functions.
  • Cellular antiviral factors can contribute to the discovery and development of therapeutical solutions against HIV-1.

Biography:

Mr. HERTEL studied in Biology at the University of Auvergne, France and graduated in 2020. He is currently working on his PhD at University of Montpellier, France in the research group of Dr. Picas at the Institute of Research in Infectiology of Montpellier, under the supervision of Dr. Blanchet, and contributed to 1 published paper while working on his PhD thesis.

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