Two Nature papers, published online, shed crucial light on the earliest events in the human body after an HIV infection. The findings may require a rethink of strategies to design HIV drugs and vaccines.
HIV gradually infects and destroys disease-fighting cells called CD4+ T cells in the blood - but in recent years scientists have discovered that it also causes a fast and dramatic loss of CD4+ T cells from mucosal surfaces such as the gut during the initial phase of infection.
By studying monkeys infected with simian immunodeficiency virus (SIV), groups led by Mario Roederer and Ashley Haase now show that the virus infects and kills a subset of these CD4+ T cells called memory CD4+ T cells, which are responsible for remembering previous infections and rapidly mobilizing a response if the body encounters the infecting agent again.
Roederer found that SIV infects 30-60% of memory CD4+ T cells within days of infection, eventually resulting in the destruction of around one-half of all memory CD4 T cells - those from mucosal tissues, lymph nodes and the blood. Haase and his colleagues show that in addition to killing by direct infection the virus also triggers the death of uninfected cells by inducing them to commit cell suicide.
These findings have important implications for the design of effective vaccines or drug therapy, which must be aimed at preventing this massive destruction of memory CD4+ T cells by reducing viral load at the early stage of infection.
Mario Roederer (National Institutes of Health, Bethesda, MD, USA)
Ashley Haase (University of Minnesota Medical School, Minneapolis, Minnesota, MN, USA)
(C) Nature press release.
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