Dr. Wei Chun Goh, an infectious-disease fellow in Dr. Michael Emerman's laboratory, has been awarded more than $88,000 from the American Foundation for AIDS Research.
Goh plans to use the grant to identify drugs that may inhibit replication of HIV, the virus that causes AIDS.
The grant, one of 13 awarded nationally, was part of an initiative to identify potential cellular and viral targets for the development of novel anti-HIV drugs. The newly funded projects will examine genes and gene products of HIV, as well as human cellular components required for HIV to thrive.
Drugs that interfere
While most anti-HIV drugs have targeted two viral enzymes - reverse transcriptase and protease - Goh plans to look for drugs that interfere with components of the host cell cycle, which Emerman's lab has shown to be important for viral replication.
"We know from work in our laboratory that HIV replication is closely linked to the cell cycle of the infected cell," she said. "Our idea is to identify drugs that manipulate the cell cycle, inhibiting replication of the virus."
In a study led by Goh, Emerman's lab published a report in 1998 demonstrating that a viral protein called vpr enhances viral reproduction by causing infected cells to stall in a portion of the cell cycle known as G2, a stage most favorable for the virus to multiply.
The cell cycle, an ordered series of events culminating in cell division is regulated by proteins known as checkpoints, which monitor steps in the cycle for errors before allowing passage to the next set of events.
"We'd like to test drugs that overcome the G2 checkpoint, allowing cells to move through the cell cycle and overcome the viral reproductive advantage," Goh said.
Goh said the types of drugs that will be tested in her study have been studied primarily in cancer cells.
A problem with drugs that act against the viral enzymes, including reverse transcriptase and protease, is that resistant viral strains emerge rapidly, because the virus develops mutations that render it insensitive to the drugs. Resistant strains multiply in the presence of the drug.
"The hope is that we can minimize problems with resistance by targeting host cell enzymes, which are more stable than viral enzymes," Goh said.
Although this strategy would not eliminate virus from the cell, they would keep viral reproduction to very low levels, Goh said. Ultimately, such drugs might be used in conjunction with more conventional antiviral therapies.
The American Foundation for AIDS Research is a nonprofit organization dedicated to the support of HIV/AIDS research, AIDS prevention, treatment education, and the advocacy of sound AIDS-related public policy.