The protein product of one of these accessory genes -- vpr -- is found in significant quantities in the extracellular free virus, suggesting that it may be crucial in the early stages of infection by the virus.
Now, researchers at the University of Pennsylvania Medical Center report that Vpr, the protein product of vpr, blocks the production of cytokines in the cells first infected by HIV, called macrophages, thus blunting immune activation of these cells. Cytokines are chemicals used by the immune system to initiate and control much of the its response to infection.
Additionally, the investigators found that Vpr is able to prevent apoptosis -- or programmed cell death -- in the infected cells, thus preserving them for use as viral production factories. And, in a further blow to the body's ability to defend against the infection, Vpr actively induces apoptosis in neighboring immune system cells that have not yet been infected, known as CD4 T cells. It also interferes with the ability of those cells to proliferate. The new findings appear in the October issue of Nature Medicine.
"In the test tube, Vpr suppresses production of the cytokines needed to
fight any infection, bacterial or viral," says David B. Weiner, PhD, senior
author and an associate professor of pathology and laboratory medicine. "It also
prevents apoptosis in the cells it infects, so those cells can stay alive to
make more virus. And then it kills the uninfected cells that would otherwise be
involved in providing
Contact: Franklin Hoke or Karen Kreeger
University of Pennsylvania School of Medicine