Roughly 5 percent of people in the world are immune to HIV and dubbed "elite controllers." This term isn’t a statement about their personalities, but a commentary about how their cells control replication of the HIV virus.
“When elite controllers are exposed to the HIV virus, they are just fine without any drugs or treatment,” said Yong-Hui Zheng, assistant professor in the Department of Microbiology and Molecular Genetics. “Our primary focus right now is to understand why these people are so resistant to the virus.”
Zheng has spent 10 years exploring this phenomenon and has discovered several proteins that have anti-retroviral properties in humans. The family APOBEC3 proteins prevent the HIV virus from replicating.
The known proteins in the APOBEC3 family have led Zheng to suggest that humans have natural defenses that can stop HIV virus replication. However, the virus has evolved a viral infectivity factor which prevents these proteins from working in patients.
Zheng has been studying HIV resistance since his postdoctoral research at Vanderbilt University and the University of California, San Francisco. He came to Michigan State in 2005, and his research is funded by the National Institutes of Health.
“Right now, my real thrust is to identify host genes with anti-HIV activity that the virus cannot take care of,” Zheng said. “Naturally occurring resistance is the best way for us to learn how to inhibit viral replication. No matter how smart human beings become, we can never beat nature. Nature has the best solutions and we must learn from these.”
Identifying naturally resistant elite controllers can be difficult, as directly testing for resistance in humans is not an option. Instead, Zheng searches for resistance in human T-cell culture lines.
“We successfully identified a T-cell line that was highly resistant,” Zheng said. “We saw a 100-fold or even a 1,000-fold decrease in viral replication in the resistant cell line. We don’t know what it is yet, but it is very, very powerful since it restricts HIV replication so strongly.”
Currently, Zheng along with his postdocs and students are testing the resistant cell line to determine what is preventing the HIV virus from replicating. Once they better understand what gives this cell line resistance, they will begin looking for this factor in the general population.
“Everybody in my lab is so excited,” Zheng said. “We’re trying to really identify this factor, to understand how it works, and ultimately develop a new treatment strategy once this factor has been identified. This is leading-edge science where we can have a great impact.”
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