Department of Medical Biology
Canada Research Chair in
(Tier 1 level)
Laval University Research Center in Infectious Diseases,
RC709 CHUL Research Center (CHUQ)
2705 Laurier Boulevard
Quebec (QC), Canada, G1V 4G2
It is now well established that the life cycle of human immunodeficiency virus type 1 (HIV-1) is intimately related to the activation state of the host immune system. Although activation of the normal immune response to invading pathogens is essential to mount a protective response, paradoxically this may also provide an immunological environment that actually drives virus replication in HIV-1-infected persons.
The central objective of one of our research projects is to shed light on the various complex effects on HIV-1 immunopathogenesis of the protozoan parasite Leishmania because it is estimated that one-third of persons infected with HIV-1 worldwide lives in endemic areas of leishmaniasis infection. Given that key pathogenesis events and most HIV-1 replication take place in lymphoid tissues and primary cultures of suspended peripheral blood lymphocytes alone can neither mimic the full cellular repertoire within lymphoid tissue nor reproduce the intimate association between cells and the stroma, we are using a well-defined experimental system made of ex vivo-infected human lymphoid tissue. We are testing if Leishmania can modulate HIV-1 transcriptional activity and virus production in human lymphoid tissues and monocyte-derived macrophages. We are also testing the capacity of HIV-1 to affect the growth of Leishmania using parasites stably expressing the firefly luciferase reporter gene or the green fluorescent protein. Interestingly, a possible link in the dangerous liaison between HIV-1 and Leishmania has been recently uncovered by demonstrating that both human pathogens exploit the dendritic cell-specific surface receptor DC-SIGN to gain entry into dendritic cells (DCs). Monocyte-derived DCs are thus used to define whether Leishmania by virtue of its capacity to interact with DC-SIGN can impair transmission of HIV-1 in trans to target CD4+ T cells. We are also investigating for a possible modification of the gene expression program in immature DCs following a pulsing with Leishmania, HIV-1, or both pathogens.
The strength of this project is that we are deciphering the complex possible interactions between HIV-1 and Leishmania using experimental models that closely recapitulate the natural in vivo reservoir of both HIV-1 and Leishmania.
Andreani G, Lodge R, Richard D, Tremblay MJ.
Mechanisms of interaction between protozoan parasites and HIV. Curr Opin HIV AIDS. 2012 Mar 14. [Epub ahead of print]
Lodge R, Ouellet M, Barat C, Andreani G, Kumar P, Tremblay MJ.
HIV-1 Promotes Intake of Leishmania Parasites by Enhancing Phosphatidylserine-Mediated, CD91/LRP-1-Dependent Phagocytosis in Human Macrophages. PLoS One. 2012;7(3):e32761. Epub 2012 Mar 6.
Bertin J, Barat C, Méthot S, Tremblay MJ.
Interactions between prostaglandins, leukotrienes and HIV-1: possible implications for the central nervous system. Retrovirology. 2012 Jan 11;9:4.
Jalaguier P, Turcotte K, Danylo A, Cantin R, Tremblay MJ.
Efficient production of HIV-1 virus-like particles from a mammalian expression vector requires the N-terminal capsid domain. PLoS One. 2011;6(11):e28314. Epub 2011 Nov 30.
St-Pierre C, Ouellet M, Giguère D, Ohtake R, Roy R, Sato S, Tremblay MJ.
Galectin-1-specific inhibitors as a new class of compounds to treat HIV-1 infection. Antimicrob Agents Chemother. 2012 Jan;56(1):154-62. Epub 2011 Nov 7.
Raymond F, Boisvert S, Roy G, Ritt JF, Légaré D, Isnard A, Stanke M, Olivier M, Tremblay MJ, Papadopoulou B, Ouellette M, Corbeil J.
Genome sequencing of the lizard parasite Leishmania tarentolae reveals loss of genes associated to the intracellular stage of human pathogenic species. Nucleic Acids Res. 2012 Feb;40(3):1131-47. Epub 2011 Oct 13.
St-Pierre C, Manya H, Ouellet M, Clark GF, Endo T, Tremblay MJ, Sato S.
Host-soluble galectin-1 promotes HIV-1 replication through a direct interaction with glycans of viral gp120 and host CD4. J Virol. 2011 Nov;85(22):11742-51. Epub 2011 Aug 31.
Barat C, Pepin J, Tremblay MJ.
HIV-1 replication in monocyte-derived dendritic cells is stimulated by melarsoprol, one of the main drugs against human African trypanosomiasis. J Mol Biol. 2011 Jul 29;410(5):1052-64.