Viral protein R (Vpr), produced by the human immunodeficiency virus (HIV), can induce oxidative stress pathway leading to cell dysfunction and even cell death, according to Temple University researchers.

The researchers published their findings, “Activation of oxidative stress pathway by HIV-1 Vpr leads to induction of hypoxia inducible factor 1 alpha expression,” in the Journal of Biological Chemistry.

“Oxidative stress is caused when the level of oxygen radicals (reactive oxygen molecules) is disturbed within the cells,” said Bassel E. Sawaya, associate professor of neurology in Temple’s School of Medicine and the lead researcher in the study.  “When the levels get too high and the antioxidants can’t create a balance, the cells begin to function improperly.”

Sawaya said that in their study, the researchers looked to answer a simple question: can HIV induce oxidative stress?  “If the answer is yes, then which protein is involved in this induction, and if we identify the protein, the third question becomes how it does induce oxidative stress?” he said.

Sawaya said that the answer to the first question is yes, HIV can induce oxidative stress.  As for which protein can do this, he said several viral proteins were shown to be involved in such phenomenon, but the researchers quickly focused on Vpr.

“We found that Vpr, which is a multifunctional protein and also known to play a role in cell death, can induce oxidative stress through two ways: one is direct, the other is indirect,” he said.  “The direct way is by activating hypoxia-inducible factor 1 alpha (HIF-1a), a transcription factor that is induced in response to low oxygen levels (hypoxia), leading to changes in gene expression. The indirect way is by Vpr activating several cellular pathways (such as TNFa and p38MAPK), which leads to an imbalance in the levels of free radicals in the cells.”

Sawaya finally added that: “with this study we’ve at least put our hands on something which will partially enhance our understanding on how HIV works in the brain, and will help in deciphering the mechanisms leading to the development of neuroAIDS.

The study was conducted in Temple’s Center for Neurovirology in collaboration with researchers from Temple’s Departments of Neuroscience and Biology.  It was funded through grants from the National Institutes of Health.