Protein Discovery Helps Explain the Body’s Failure to Kill HIV

jason

Seanchaí
Staff member
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.

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Casey

MM, RAM, 32nd.
HIV is a fascinating virus. It should be nothing for the body to kill it- a simple enveloped virus, completely incapable of survival outside the body, should be easier to put on ice than the cold.

Finding a way to bring NK cells into play is an interesting idea. Another I have heard is genetic therapy, introducing white blood cells that are free of the CCR5 receptor, the receptor that HIV uses to bind. In theory, a person then could be infected with the virus, but given no place to replicate, the virus would quickly die.

This very thing has been seen in a small subset of Thai prostitutes who are CCR5-negative- they can have massively high HIV viral loads, but never have the disease itself. The virus can get in, but it's like being trapped in a padded cell- it just runs around until it dies.
 
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