HIV Inhibitor Blocks Infection

Research may lead to targeted therapeutic approach.

HIV infection may be able to be blocked by attacking the protective capsule of the virus called the capsid, according to a recent study.

Published on December 15, 2014 in Proceedings of the National Academy of Sciences, the study examined the vital role played by the capsid, which surrounds the HIV-1 genome. The capsid must disassemble when the virus enters the cell to release the disease-causing load at the right time and place.

"It's still a matter of debate at what point the capsid falls apart in HIV-1 infection of cells," senior author Dmitri Ivanov, PhD, said in a press release.

The study indicates how HIV inhibitor PF74 and the host protein CPSF6 bind to the capsid surface in a small pocket to block it from disassembling. As a result of this process, the viral information is kept inside.

"We think that this process can be targeted for therapeutic purposes in HIV-1 infections," Dr. Ivanov said.

The researchers utilized X-ray crystallography in order to examine the three-dimensional structure of the CPSF6 protein that binds to the capsid.

"Seeing molecules in 3-D is illuminating; it tells us something about their function," Dr. Ivanov said. "We now know how PF74 and CPSF6 interact with the adjacent building blocks of the HIV-1 capsid, thus stabilizing the entire capsid structure. It tells us that these molecules bind to the capsid before disassembly, blocking viral replication."