Scientists at the Gladstone Institute of Virology and Immunology have been able to solve a long-standing mystery about HIV infection as to how the virus promotes the death of CD4 T cells.
The study reveals that the virus actually makes an entry into the CD4 T cells to make a DNA copy of its reverse transcription, according to Dr. Gilad Doitsh, who performed many of the studies and is the lead author of the paper.
The researchers identified the precise step in which the CD4 T cells die by using different anti-HIV drugs to arrest the virus at different points in its life cycle. Drugs that blocked viral entry or that blocked the start of reverse transcription stopped the killing.
Conversely, drugs that acted later in the life cycle did not. Importantly, the researchers used primary human lymphoid tissues, such as tonsil and spleen to uncover this death pathway. These and other lymphoid tissues contain over 98pc of the body’s CD4 T cells and represent the major site where the virus reproduces itself.
The team also found that the dying cells do not go silently into the night. As they die, these cells release proteins, called cytokines, that cause inflammation and that attract healthy cellular targets promoting repeated rounds of infection and cell death. Scientists have long been interested in why HIV infection and inflammation seem to go hand in hand. This study reveals a new mechanism linking the virus to inflammation.
The findings have been reported in the November 24th issue of Cell, a Cell Press publication.
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