The AIDS virus (HIV) attacks immune system cells and once inside them it multiplies. In some of these immune cells, viral stocks are not very accessible to antiviral therapy. CNRS, Institut Curie and Institut Pasteur researchers investigating how HIV avoids being destroyed by immune cells have discovered that HIV alters the pH of the cellular compartments where it accumulates, thus stopping the activation of the very enzymes that would normally degrade it.
When viruses or infectious bacteria enter our body, the immune system is triggered to eliminate them, through a process involving various types of white blood cells. Some viruses target the immune system. For example, HIV (human immunodeficiency virus) attacks two sorts of white blood cells: macrophages, which play an early role in immune defense by phagocytosing and then digesting the invader, and certain lymphocytes (CD4 T lymphocytes), which come into play later in the immune response. HIV accumulates in the infected macrophages, which are veritable viral reservoirs pretty much inaccessible to antiviral treatments. Multiplication of HIV destroys the CD4 T lymphocytes.
At the Institut Curie, Philippe Benaroch, CNRS Director of Research, and his Intracellular Transport and Immunity group in the Inserm laboratory (1), have been studying the immune system and how it breaks down. They have investigated the proliferation of HIV in macrophages, in collaboration with their colleagues in the Virus and Immunity Laboratory of the Institut Pasteur associated with the CNRS(2). They have shown that the viral particles accumulate in certain compartments of the infected macrophages. Now, these compartments normally have an acid pH at which HIV shouldn’t survive. But pH measurements have revealed that HIV manages to impair the acidification of these compartments and so create an environment where it can survive and multiply. In these compartments, the enzymes that degrade viruses need an acid pH to work effectively, and so are put out of action by the change in pH produced by HIV. By controlling its environment, HIV can multiply within the infected macrophages, where compartments not containing viral proteins or particles seem to function normally.
This study sheds new light on how HIV remains infectious for long periods of time in infected patients, and points the way to the identification of new therapeutic targets for the elimination of viral stocks in macrophages.
Article: Cell Host and Microbe, issue 16 August 2007