Michel Tremblay

Professor

Department of Medical Biology
Canada Research Chair in
Human Immuno-Retrovirology
(Tier 1 level)

Laval University Research Center in Infectious Diseases,
RC709 CHUL Research Center (CHUQ)
2705 Laurier Boulevard
Quebec (QC), Canada, G1V 4G2

Tel: (418) 654-2705,
Fax: (418) 654-2212
Michel [dot] J [dot] Tremblay [at] crchul [dot] ulaval [dot] ca (Email)

Research Interests

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.

Selected publications

Leishmania - HIV Puplications

Garg R, Trudel N, Tremblay MJ. (2007)

Consequences of the natural propensity of Leishmania and HIV-1 to target dendritic cells. Trends Parasitol. 23: 317-324.

Barat C, Zhao C, Ouellette M, Tremblay MJ. (2007)

HIV-1 replication is stimulated by sodium stibogluconate, the therapeutic mainstay in the treatment of leishmaniasis. J Infect Dis. 195:2 36-45.

Breton M, Zhao C, Ouellette M, Tremblay MJ, Papadopoulou B. (2007)

A recombinant non-pathogenic Leishmania vaccine expressing human immunodeficiency virus 1 (HIV-1) Gag elicits cell-mediated immunity in mice and decreases HIV-1 replication in human tonsillar tissue following exposure to HIV-1 infection. J Gen Virol. 88(Pt 1): 217-25.

Provost P, Barat C, Plante I, Tremblay MJ. (2006)

HIV-l and the microRNA-guided silencing pathway: an intricate and multifaceted encounter. Virus Res. 121: 107-15.

Zhao, C., Thibault, S., Messier, N., Ouellette, M., Papadopoulou, B., Tremblay, M.J. (2006)

"In primary human monocyte-derived macrophages exposed to HIV-1, does the increased intracellular growth of Leishmania infantum rely on its enhanced uptake?" J Gen Virol 87 (5): 1295-1302.

Breton M, Tremblay MJ, Ouellette M, Papadopoulou B.(2005)

Live nonpathogenic parasitic vector as a candidate vaccine against visceral leishmaniasis. Infect Immun. 73: 6372-82.

Zhao, C., Cantin, R., Breton, M., Papadopoulou, B., Tremblay, M.J. (2005)

"DC-SIGN-mediated transmission of HIV-1 is compromised by the ability of Leishmania infantum to exploit also DC-SIGN as a ligand", Journal of Infectious Diseases 191 (10), 1665-1669.

Zhao, C., Papadopoulou, B., Tremblay, M.J. (2004)

"Leishmania infantum enhances human immunodeficiency virus type-1 replication in primary human macrophages through a complex cytokine network", Clinical Immunology 113 (1), 81-88.

Zhao, C., Papadopoulou, B., Tremblay, M.J. (2004)

"Leishmania infantum promotes replication of human immunodeficiency virus type 1 in human lymphoid tissue ex vivo by inducing secretion of the proinflammatory cytokines TNF-alpha and IL-1alpha", Journal of Immunology 172 (5), 3086-3093.

HIV Publications:

Barat C, Martin G, Beaudoin AR, Sevigny J, Tremblay MJ. (2007)

The Nucleoside Triphosphate Diphosphohydrolase-1/CD39 Is Incorporated into Human Immunodeficiency Type 1 Particles, Where It Remains Biologically Active. J Mol Biol. May 10; [Epub ahead of print]

Martin G, Roy J, Barat C, Ouellet M, Gilbert C, Tremblay MJ. (2007)

Human immunodeficiency virus type 1-associated CD40 ligand transactivates B lymphocytes and promotes infection of CD4(+) T cells. J Virol. 81: 5872-81.

Sun J, Barbeau B, Tremblay MJ.(2006)

HIV-1-mediated syncytium formation promotes cell-to-cell transfer of Tax protein and HTLV-I gene expression.Virus Res.118: 120-9.

Vidricaire G, Tremblay MJ.(2005)

Rab5 and Rab7, but not ARF6, govern the early events of HIV-1 infection in polarized human placental cells.J Immunol. 175: 6517-30.

Tardif MR, Tremblay (2005)

MJ. Related Articles, Links LFA-1 is a key determinant for preferential infection of memory CD4+ T cells by human immunodeficiency virus type 1.J Virol. 79: 13714-24.

Gilbert C, Bergeron M, Methot S, Giguere JF, Tremblay MJ. (2005) Statins could be used to control replication of some viruses, including HIV-1.Viral Immunol. 18:474-89. Review.

Giguere JF, Diou J, Madrenas J, Tremblay MJ.(2005)

Virus attachment and replication are promoted after acquisition of host CD28 and CD152 by HIV-1. J Immunol. 175: 926-35.

Pare ME, Gauthier S, Landry S, Sun J, Legault E, Leclerc D, Tanaka Y, Marriott SJ, Tremblay MJ, Barbeau B. (2005)

A new sensitive and quantitative HTLV-I-mediated cell fusion assay in T cells. Virology. 338: 309-22.

Cantin, R., Méthot, S., Tremblay, M.J. (2005)

"Plunder and stowaways: Incorporation of cellular proteins by enveloped viruses", Journal of Virology 79 (11), 6577-6587.

Martin, G., Beauséjour, Y., Thibodeau, J., Tremblay, M.J. (2005)

"Envelope glycoproteins are dispensable for insertion of host HLA-DR molecules within nascent human immunodeficiency virus type 1 virions" Virology 335 (2), 286-290.

Roy, J., Martin, G., Giguère, J.-F., Bélanger, D., Pétrin, M., Gilbert, C., Tremblay, M.J. (2005)

"Human Immunodeficiency Virus type 1 can act as an antigen-presenting cell upon acquisition from the host cell of peptide-loaded HLA-DR and CD86 molecules", Journal of Immunology 174 (8), 4779-4788.

Ouellet, M., Bounou, S., Pelletier, I., Roy, J., Mercier, S., Hirabayashi, J., Sato, S., Tremblay, M.J. (2005)

"Galectin-1 acts as a soluble host factor that promotes HIV-1 infectivity through stabilization of virus attachment to host cells", Journal of Immunology 174 (7), 4120-4126.

Tardif, M.R., Tremblay, M.J. (2005)

"Tetraspanin CD81 provides a co-stimulatory signal resulting in an increased human immunodeficiency virus type 1 gene expression in primary CD4+ T lymphocytes through NF-kappa B, NFAT and AP-1 transduction pathways", Journal of Virology 79 (7), 4316-4328.

Sun, J., Bergeron, M., Barbeau, B., Boivin, G., Tremblay, M.J. (2005)

"Influenza virus activates human immunodeficiency virus type-1 gene expression in human CD4-expressing T cells through an NF-kappa B-dependent pathway", Clinical Immunology 114 (2), 190-198.

Beauséjour, Y., Tremblay, M.J. (2004)

"Interaction between the cytoplasmic domain of ICAM-1 and Pr55Gag leads to acquisition of host ICAM-1 by HIV-1", Journal of Virology 78 (21), 11916-11925.

Vidricaire, G., Imbeault, M., Tremblay, M.J. (2004)

"The endocytic host cell machinery plays a dominant role in the intracellular trafficking of incoming HIV-1 in human placental trophoblasts", Journal of Virology 78 (21), 11904-11915.

Giguère, J.-F., Tremblay, M.J. (2004)

"Statin compounds reduce HIV-1 replication by preventing the interaction between virion-associated host ICAM-1 with its natural cell surface ligand LFA-1", Journal of Virology 78 (21), 12062-12065.

Fortin, J.-F., Barat, C., Beauséjour, Y., Barbeau, B., Tremblay, M.J. (2004)

"Hyper-responsiveness to stimulation of human immunodeficiency virus-infected CD4+ T cells to stimulation requires Nef and Tat virus gene products and results from higher NFAT, NF-kappa B, and AP-1 induction", Journal of Biological Chemistry 279 (38), 39520-39531.

Beauséjour, Y., Tremblay, M.J. (2004)

"Susceptibility of HIV type 1 to the fusion inhibitor T-20 is reduced on insertion of host intercellular adhesion molecule 1 in the virus membrane", Journal of Infectious Diseases 190 (5), 894-902.

Martin, G., Tremblay, M.J. (2004)

"HLA-DR, ICAM-1, CD40, CD40L and CD86 are incorporated to a similar degree into clinical human immunodeficieny virus type 1 variants expanded in natural reservoirs such as peripheral blood mononuclear cells and human lymphoid tissue cultured ex vivo", Clinical Immunology 111 (3), 275-285.

Bounou, S., Giguère, J.-F., Cantin, R., Gilbert, C., Imbeault, M., Martin, G., Tremblay, M.J. (2004)

"The importance of virus-bound host ICAM-1 in HIV-1 transfer depends on the cellular context", FASEB Journal 18 (11), 1294-1296 /

Beauséjour, Y., Tremblay, M.J. (2004)

"Envelope glycoproteins are not required for insertion of host ICAM-1 into human immunodeficiency virus type 1 and ICAM-1-bearing viruses are still infectious despite a suboptimal level of trimeric envelope proteins", Virology 324 (1), 165-172.

Barat, C., Gervais, P., Tremblay, M.J. (2004)

"Engagement of ICAM-3 provides a co-stimulatory signal for human immunodeficiency virus type 1 replication in both quiescent and activated CD4+ T lymphocytes: Implications for virus pathogenesis", Journal of Virology 78 (12), 6692-6697.

Giguère, J.-F., Bounou, S., Paquette, J.-P., Madrenas, J., Tremblay, M.J. (2004)

"Insertion of host-derived costimulatory molecules CD80 (B7.1) and CD86 (B7.2) into human immunodeficiency virus type 1 affects the virus life cycle", Journal of Virology 78 (12), 6222-6232.

Publications - Michel J. Tremblay