HIV – theory of T cell loss questionable
HIV’s Effect On White Blood Cells Questioned By New Research
Scientists have refuted a longstanding theory of how HIV slowly depletes the body’s capacity to fight infection, in new research.
The AIDS virus causes disease by inactivating the body’s immune responses. Most severely affected are the white blood cells known as T lymphocytes, particularly the CD4+ T cells that recognize infection and enable other cells of the immune system to respond against it. Following rapid loss in the first few weeks of HIV infection, the number of CD4+ cells in the blood falls slowly, often over a period of ten years or longer. The exact mechanisms by which CD4+ cell depletion occurs are not fully understood.
It has long been a major puzzle why this process of depletion is so slow, often taking 10 years or more.
One popular theory has been the “runaway” hypothesis, which says that T cells infected by HIV produce more HIV virus particles, which activate more T cells, that in turn become infected, leading to an uncontrolled cycle of T cell activation, infection, HIV production and cell destruction.
However, this new study in PLoS Medicine shows that this theory cannot explain the very slow pace of depletion that occurs in HIV infection. The research team used a mathematical model of the processes by which T cells are produced and eliminated to show that if the runaway theory was correct, then T helper cell numbers would fall to very low levels over a number of months, not years.
One of the paper’s authors is Jaroslav Stark, Professor of Mathematics at Imperial College London, and Director of the Centre of Integrative Systems Biology at Imperial. He said: “Scientists have never had a full understanding of the processes by which T helper cells are depleted in HIV, and therefore they’ve been unable to fully explain why HIV destroys the body’s supply of these cells at such a slow rate. Our new interdisciplinary research has thrown serious doubt on one popular theory of how HIV affects these cells, and means that further studies are required to understand the mechanism behind HIV’s distinctive slow process of cellular destruction.”
The research team think that one possible explanation could be that the virus slowly adapts itself over the course of the infection, but they stress that further analysis is needed to verify this alternative theory.
Professor Stark adds: “If the specific process by which HIV depletes this kind of white blood cells can be identified, it could pave the way for potential new approaches to treatment.”
Understanding the Slow Depletion of Memory CD4+ T Cells in HIV Infection
Yates A, Stark J, Klein N, Antia R, Callard R
PLoS Medicine Vol. 4, No. 5, e177 doi:10.1371/journal.pmed.0040177