New publication from CanCURE Theme 2 co-Leader Jérôme Estaquier
The introduction of combined antiretroviral therapy (cART) in the treatment of HIV infection in the 1990s has dramatically changed the course of this disease. However, the persistence of viral DNA within host cells is one of the main obstacles to eradicate the virus, associated with chronic inflammation.
Like the Hydra of Lerne each cell, each tissue, represents in itself a fight to eliminate viral-infected cells, but which at each interruption of ART is reborn from these sanctuaries.
Ceramic showing the Hydra of Lerna, represented by a serpent with many heads,
and his fight against Heracles.
In this context, and because there is an early spread of the virus within the body, we searched to identify cell and tissue sanctuaries by focusing on CD4 T cells, target of HIV. Thus, we have administrated at day 4 post-infection a therapy consisting of two inhibitors of reverse transcriptase, an integrase inhibitor, and an HIV protease inhibitor that can also potentiate the effects of other drugs.
Early administration was aimed to limit viral spread and reduce the number of "heads" to explore. Thus, despite the absence of infected CD4 T cells in the blood and peripheral lymph nodes, there is a viral rebound indicating the early establishment of these reservoirs in other organs. By this approach, and after isolating T lymphocytes, our study shows that we detect viral DNA in a fraction of CD4 T lymphocytes. The population is mainly related to memory CD4 T cells, in particular a cell which is essential for B cells and the production of antibodies. The establishment of these reservoirs is observed in visceral tissues including the spleen and the mesenteric lymph nodes that drain the small (jejunum and ileum) and large (colon) intestines. The detection of early reverse transcripts indicates also a low level of viral replication despite ART
Thus, the identification of these cells is a key element in our understanding of viral reservoirs and therapeutic approaches to AIDS. The perspectives are immense, because they make it possible to imagine new strategies able to target these tissues and more specifically these T cells, and to better understand the mechanisms of escape and emergence of resistance. Moreover, because due to the role of T follicular helper cells, which are early targets of the virus, strategies aim to prevent their infection could be helpfully for vaccinal strategies.
These studies supported by the Canadian HIV cure enterprise (CanCURE), the Canadian Institutes of Health Research (CIHR) and the French Agency for Research on AIDS and Viral Hepatitis are part of the international effort to find ways of eradicating HIV.