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New HIV Model Shows Virus Doesn't Kill White Blood Cells, It Just Homes Them To Death

Date:
September 18, 2000
Source:
University Of Michigan
Summary:
University of Michigan scientist Denise Kirschner has developed a new mathematical model that shows how HIV---the virus that causes AIDS---slowly destroys its victim's immune system by accelerating a normal process called homing, which diverts white blood cells from the bloodstream to the lymph system.

ANN ARBOR---University of Michigan scientist Denise Kirschner has developed a new mathematical model that shows how HIV---the virus that causes AIDS---slowly destroys its victim's immune system by accelerating a normal process called homing, which diverts white blood cells from the bloodstream to the lymph system.

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Increased understanding of the complex relationship between the HIV virus and the immune system is important, because it will help scientists develop more effective treatments for AIDS and suggest new targets for therapeutic drugs.

"This model indicates that the key to extending survival time for people with AIDS is to minimize the number of CD4 cells exposed to signals in the lymph system which lead to apoptosis or cell suicide," says Miles W. Cloyd, Ph.D., a professor of microbiology at the University of Texas Medical Branch at Galveston.

Developed in collaboration with G.F. Webb, Ph.D., of Vanderbilt University, Kirschner's model validates the homing theory of HIV progression, which was first proposed by Cloyd and his colleagues. Results from the model were published in the August 1 issue of The Journal of AIDS.

Many scientists believe HIV destroys the immune system by attacking white blood cells called CD4 or helper T-cells in the bloodstream. But Kirschner and Cloyd maintain that HIV's lethal action is much more subtle and indirect.

Their model shows that CD4 cells actually self-destruct in the lymph system. Death comes as a result of exposure to biochemical signals involved in the homing process, which trigger apoptosis or cell suicide.

"Previous HIV models have focused on what happens in the bloodstream, but the real action is in the lymph system," says Kirschner, Ph.D., an assistant professor of microbiology and immunology in the U-M Medical School. "A very small percentage of cells dies from apoptosis on a daily basis, but over a seven-year period, it adds up to almost 100 percent."

Results from the U-M model are consistent with what happens in people, according to Cloyd. Data from clinical studies with HIV-infected patients show that the population of uninfected CD4 cells in their blood falls to 15 percent of normal during a seven-year period.

When the HIV virus binds to a CD4 cell, one of three things can happen, according to Kirschner. First, the cell can be actively infected and turn into a cellular factory that produces more virus. Second, the immune cell can be latently infected; the virus gets inside the cell nucleus, but remains dormant. Third, and most common, the CD4 cell can be abortively infected. In this case, the virus enters the cell cytoplasm, but doesn't enter the nucleus.

"When the HIV virus binds to a CD4 cell, the process activates a receptor molecule called L-selectin on the cell membrane, which signals the CD4 cell to home to the lymph system," Kirschner explains. "If we could block that signal, we could preserve healthy CD4 cells."

In future research, Kirschner plans to model the role of co-receptors involved in HIV binding to CD4 cells. The virulence of infection varies depending on the co-receptor chosen by the virus. She also plans to explore the immune response to HIV, and how different types of immune responses, known as TH1 or TH2 responses, determine disease progression.

"Miles Cloyd's work has brought the concept of lymphocyte circulation, which was a hot topic in the 1970s, back into the scientific limelight," she says. "There could be applications to many other diseases."

Development of the mathematical model of HIV progression was funded by the National Heart, Lung and Blood Institute of the National Institutes of Health, the National Science Foundation and the American Foundation for AIDS Research.


Story Source:

The above story is based on materials provided by University Of Michigan. Note: Materials may be edited for content and length.


Cite This Page:

University Of Michigan. "New HIV Model Shows Virus Doesn't Kill White Blood Cells, It Just Homes Them To Death." ScienceDaily. ScienceDaily, 18 September 2000. <www.sciencedaily.com/releases/2000/09/000913203858.htm>.
University Of Michigan. (2000, September 18). New HIV Model Shows Virus Doesn't Kill White Blood Cells, It Just Homes Them To Death. ScienceDaily. Retrieved November 23, 2014 from www.sciencedaily.com/releases/2000/09/000913203858.htm
University Of Michigan. "New HIV Model Shows Virus Doesn't Kill White Blood Cells, It Just Homes Them To Death." ScienceDaily. www.sciencedaily.com/releases/2000/09/000913203858.htm (accessed November 23, 2014).

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