DCIR, a new therapeutic target for preventing HIV-1 infection
It is estimated that 1,8 million persons are newly infected by HIV-1 each year. Pre-exposure prophylaxis (PrEP) with oral antiretroviral drugs can be used to reduce the risk of infection by this virus. Hence, focussing on new therapeutic targets might provide alternative options to prevent HIV-1 infection.
Dendritic cells are the first immune cells recognizing HIV-1 in mucosal tissues and the initial interaction occurs through attachment factors and the dendritic cell immunoreceptor (DCIR). The binding of HIV-1 to DCIR allows the virus to be internalized before an immune response can be elicited.
In an effort to develop new therapeutic options against HIV, the team of Prof Gilbert has been testing a collection of compounds which could block the binding of HIV-1 to DCIR, without affecting the specific immune responses. Antagonizing DCIR might also prove useful in the treatment of tuberculosis, malaria, autoimmune diseases, and asthma.
Gilbert C, MJ Tremblay, S-X Lin, A Azzi, and A Lambert (2013-2017). Three-dimensional cavities of dendritic cell immunoreceptor (DCIR), compounds binding thereto and therapeutic applications related to inhibition of human immunodeficiency virus type-1 (HIV-1). CA2860015A1, US9731001B2. Assignee: Université Laval.
Borhis G, C Burelout, N Chaoul, N Smith, C Goujard, L Meyer, S Paul, H Saoudin, A Hosmalin, C Gilbert, JP Herbeuval, and Y Richard (2016). Plasmacytoid dendritic cells and myeloid cells differently contribute to B-cell-activating factor belonging to the tumor necrosis factor superfamily overexpression during primary HIV infection. AIDS 30: 365-376.
Lambert AA, A Azzi, S-X Lin, G Allaire, KP St-Gelais, MJ Tremblay, and C Gilbert (2013). Dendritic cell immunoreceptor is a new target for anti-AIDS drug development: identification of DCIR/HIV-1 inhibitors. PLoS ONE 8: e67873.
Lambert AA, F Barabé, C Gilbert, and MJ Tremblay (2011). DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway. Blood 117: 6589-6599.
Lambert AA, M Imbeault, C Gilbert, and MJ Tremblay (2010). HIV-1 induces DCIR expression in CD4+ T cells. PLoS Pathog 6: e1001188.
SOVAR and Université Laval seek a partner for chemical derivation, co-development of lead candidates, licensing, or commercialization of this technology.
The laboratory of Prof Gilbert is fully capable of evaluating derivatives or new lead compounds in vitro and in vivo, especially in humanized mouse models developed to study the role of DCIR in the pathogenesis of HIV infection.