Innocent bystander is not so innocent
7 Jan 2011 by Evoluted New Media
The long-standing mystery of how HIV promotes the death of CD4 T cells and causes AIDS has been solved by scientists in America – it’s down to “bystander cell killing”.
The long-standing mystery of how HIV promotes the death of CD4 T cells and causes AIDS has been solved by scientists in America – it’s down to “bystander cell killing”.
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Mechanism for CD4 T-cell death during HIV-infection |
The immune cells – which are seemingly not infected by HIV – are not innocent victims as scientists previously thought; they are in fact the result of failed or abortive form of viral infection. Researchers from the Gladstone Institute of Virology and Immunology studied primary human lymphoid tissue – the tonsils and the spleen – to uncover CD4 T’s death pathway, because these tissues contain over 98% of the body’s CD4T cells and is where the virus reproduces itself.
“Our study reveals that the virus actually enters the CD4 T cells that are destined to die and that the virus starts to make a DNA copy of its RNA, a process called reverse transcription,” said lead author Dr Gilad Dotish. “However, this process does not work well in the majority of these cells and the incomplete DNA intermediates that accumulate in the cytoplasm are sensed and trigger the cells to ‘commit suicide’ in an attempt to protect the body.”
By using different anti-HIV drugs to stop the virus at different points in its life cycle, researchers were able to identify the precise step in which the CD4 T cells die – drugs that blocked viral entry or the start of reverse transcription stopped the cells from being killed.
The team also found that the dying cells don’t go silently – as they die these cells release cytokines that cause inflammation and attract healthy cellular targets, promoting repeated rounds of infection and cell death.
“Our findings have revealed a completely unexpected mechanism for CD4 T-cell death during HIV-infection,” said Warner C Greene, institute director and senior author of the paper, “These results highlight how a natural cellular defence normally used by the host to repel foreign invaders goes awry in HIV infection, resulting in a profound depletion of CD4 T cells. If untreated, this process ultimately causes AIDS.”
