Researchers at Rush University Medical Center in Chicago have discovered a protein produced by HIV that keeps infected cells from signaling the immune system that they are harboring the virus and should be killed. These data, which suggest a new target for HIV drugs, were published online October 18 in the journal Cell Host & Microbe and are discussed in a release available at EurekAlert.
Among the most powerful tools in the immune system’s toolbox for killing infected or defective cells are natural killer (NK) cells. They are unlike HIV-specific CD8 cells, which require a lot of stimulation by other parts of the immune system before they can go into action. NK don’t require virus-specific stimulation before they can recognize and kill infected cells. Yet, for reasons not fully understood, they don’t work the way they should against HIV.
Given the potency of NK cells, and their potential to run amok and kill healthy cells, they must first encounter three different types of proteins on the surface of a potentially infected cell. First, an infected cell needs to express a type of receptor called a major histocompatibiliy (MHC) receptor, which indicates that the cell belongs to the person. The NK cell must also encounter a stimulatory molecule and a costimulatory molecule on the target cell’s surface. If all three of these molecules are present and bind to the corresponding NK cell receptors, then the NK cell will release a chemical that degrades the infected cell.
During the past two decades, immunologists have investigated how NK cells interact with HIV-infected cells, but researchers have long been baffled by a key finding. While the kinds of cellular proteins that are supposed to flag the cell for destruction do get made during the HIV replication process and travel to the surface of the cell, NK cells still fail to recognize and kill them.
It turned out that yet another type of protein called Natural killer T-cell and B-cell Antigen (NTB-A) is also needed at the cell’s surface to alert NK cells that the cell is infected and needs to be destroyed. In the case of HIV, the NTB-A didn’t make it to the surface. Researchers, however, found that HIV did not directly suppress the NTB-A. So why didn’t it make it to the surface to alert the killer cells?
Ankur Shah, PhD, from Rush University, and his colleagues now think they know the answer. Shah’s team found that an accessory protein made by HIV, called Vpu, keeps NTB-A from reaching the cell’s surface. Shah’s team proved this by altering the Vpu protein made by HIV in cells in test tubes and then observing what happened when they added NK cells. The NK cells were 100 times as likely to recognize and kill cells infected with HIV that produced the defective Vpu protein than those infected with HIV that produced the normal Vpu protein. “With this information, we now have a major new target for drug therapies
Source: http://www.poz.com/rssredir/articles/hiv_vpu_nkcells_761_19447.shtml
Filed under: HIV and AIDS, HIV Treatment, Medical and Research, Aids, hiv, HIV Treatment
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