could someone explain how TNF-related apoptosis-inducing ligand or TRAIL works?

Question

"Being able to selectively kill cells that harbor HIV is one of the holy grails of HIV research. Dr. Badley's group took a giant step when, in 2001, they accomplished the feat in a test tube. The experiment used a cloned apoptosis-inducing protein called TRAIL (TNF-related apoptosis-inducing ligand). In the study, which took place in Dr. Badley's native Canada, investigators took cells from HIV patients and exposed them to TRAIL in a test tube. The results were rewarding—cells that contained HIV died while HIV-negative cells lived."

Why does the TRAIL only kill the hiv cells?
Does anyone have a good explanation for how TRAIL works?

Answer 1

The soluble TRAIL protein induces cell death (apoptosis) by binding to its ligand (DR5) on the surface of its target cell. It appears that DR5 expression is higher on HIV-infected cells, therefore they are more sensitive to this mechanism of killing.

DR5 is induced on cells as a result of other inflammatory conditions not related to HIV, so TRAIL does not specifically kill HIV-infected cells. A late stages of HIV infection, many uninfected cells may also express high amounts of DR5, so bystander killing by TRAIL may pose a problem clinically.

Answer 2

Try doing a search on Pubmed. Here are quotes from a couple of papers I found in a quick search using the terms "TRAIL review".

1) "The basis of resistance to Apo2L/TRAIL induced apoptosis in malignant cells and normal cells is not completely understood, but it is known that a variety of factors including hypoxia, MMPs and cytokines present in the tumor microenvironment can influence the response of malignant cells to Apo2L/TRAIL."
- Immunol Invest., 2006;35(3):279-96

2) "...TRAIL induces apoptosis through two death receptors, death receptor 4 (DR4) and death receptor 5 (DR5), that are expressed on the cell membrane. Binding of the ligand to the death receptors leads to activation of the extrinsic apoptosis pathway."
- Eur J Cancer. 2006 Jul 31; (Epub ahead of print)

Hope this is helpful. Best wishes.

Answer 3

allz i kno is hiv be killin my brothas yo