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Two Immune Proteins Found to Control HIV Infection

By Alan McCord

January 9, 2009

A new observation in how the immune system of those who naturally control HIV without therapy may lead scientists closer to curing the disease. Recent results from a study conducted by the National Institute of Allergy and Infectious Diseases, part of the US National Institutes of Health, show that two key proteins used by CD8 cells effectively control HIV infection. The research was highlighted in the December 19 issue of Immunity.

A small percentage of people living with HIV can control the infection on their own, without using HIV drugs. Although scientists have known about these long-term non-progressors or LTNPs for some time, they have not been able to fully understand how their immune systems control HIV disease. This series of experiments continues to open doors to understanding the pathology of HIV infection.

The NIAID research used new technology to watch how CD8s interact with CD4 cells that are infected with HIV in both LTNPs and progressors whose HIV levels were comparably under control (below 50) with drugs. Results followed the activity of CD8 cells over 6 six days in lab study.

Generally speaking, CD4 cells are the "generals" that give orders to other immune cells, such as CD8s. In turn, certain CD8s carry out the task of killing those cells infected with HIV, including CD4s. Early in the research, there was little difference between the groups. However, by day 6, in the LTNPs more than 75% of the infected CD4s were killed within an hour, while only 40% of infected cells were ever killed in the progressors.

Among the LTNPs, two CD8 proteins -- perforin and granzyme B -- were at significantly higher levels than in progressors. As well, in LTNPs 68% of infected CD4s were killed by their CD8 cells compared to only 8.1% for progressors. This led the researchers to believe that it's not necessarily the number of CD8s that are needed to control HIV but how effective they are in carrying out their tasks.

The researchers believe that the CD8s in LTNPs make and use these two proteins to keep HIV more expertly under control. Perforin punctures the walls of infected CD4s while granzyme B enters those cells and kills them off. However, in progressors, their CD8s don't make or store enough of the two proteins to control their infection and disease over time.

Most of the research done on understanding how the immune system manages HIV infection has focused on the role that CD4 cells play in directing other immune cells to rid HIV from the body. Yet, they're certainly not the whole story in getting HIV under control. This study, among others, continues to show how CD8s also play critical roles in controlling infection, and may even be more important to restraining HIV from causing disease. Research such as this may lead to finding new avenues for HIV therapy, a vaccine or even a cure.

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