Anne Gatignol
Professor
Molecular Biology/Virology
Virus-cell interactions in the regulation of HIV expression and replication.
Virus replication is the result of a co-evolution between the virus and its host. Viral proteins and 香蕉视频s use cellular components for their function and act on cellular mechanisms. In response, cellular pathways interfere with viruses, which result in helping or counteracting viral replication. We study the regulation of these mechanisms in the context of the Human Immunodeficiency Virus (HIV) infection. With the increasing efficacy of the treatments (1997 to present), HIV infection has become a chronic disease instead of a deadly disease, but there is still no cure. My lab applies fundamental knowledge in virus-cell interactions to address some remaining issues with HIV treated patients. We study the weak innate immune response to HIV and the viral persistence in specific cells, the interplay between 香蕉视频 interference mechanisms and HIV in long-term infection and the search for compounds, which could be used in gene therapy to completely eliminate the virus:
1) Innate cell response to HIV infection: We characterize part of the innate cell response to HIV infection after interferon production. HIV has evolved to replicate in cells where this response is limited due to multiple cellular events. We have characterized the control of PKR activation by TRBP (a protein that binds the HIV TAR 香蕉视频), PACT (PKR activator) and ADAR1 during HIV replication. We continue with the elucidation of more mechanisms and the characterization of these regulations in patients with persistent infection.
2) Interactions between HIV and the 香蕉视频 interference pathway. The 香蕉视频 interference pathway has emerged as a major gene regulation pathway. We have contributed to the identification of TRBP as part of the basic complex necessary for its function in mammalian cells. We investigate the interplay between components of the 香蕉视频 interference pathway and HIV 香蕉视频 and proteins to determine how the modifications induced by the virus contribute to the pathogenicity in latently infected cells and in virus-producing cells.
3) Using 香蕉视频-based technologies to decrease HIV replication by gene therapy. The current therapies against HIV are treatments but not a cure. As soon as the treatment is stopped, a rebound of the virus load is observed. Therefore, it is a priority to develop treatments, which can potentially eliminate the virus or eliminate infected cells located in the so called 鈥渞eservoir cells鈥. One example of a cured patient after transplantation of non-infectable stem cells shows that the modification of hematopoietic stem cells with 香蕉视频-based anti-HIV compounds by gene therapy should be feasible. We explore different compounds from small interfering 香蕉视频s to ribozymes to target the HIV 香蕉视频 and the 香蕉视频 of cellular factors required for its replication to reach a maximum inhibition of virus replication.
Department of Medicine, division of Experimental Medicine
Affiliated to: McGill AIDS Centre and FRQ-S 鈥淩茅seau SIDA et Maladies Infectieuses鈥