FRIDAY, SEPTEMBER 30, 2016

Researchers describe HIV's protein shell for the first time

A research team led by scientists at the University of Pittsburgh School of Medicine recently became the first group to describe the four million atom structure of the HIV's protein shell.

The team used a hybrid approach of standard cryo-electron microscopy, cryo-electron tomography and a supercomputer to reveal the physical and structural characteristics of the HIV's capsid. Peijun Zhang, the senior author of the study, said the findings could result in new ways to counteract the deadly virus.

"The capsid is critically important for HIV replication, so knowing its structure in detail could lead us to new drugs that can treat or prevent the infection," Zhang said. "This approach has the potential to be a powerful alternative to our current HIV therapies, which work by targeting certain enzymes, but drug resistance is an enormous challenge due to the virus' high mutation rate."

The study, which was published in Thursday's issue of Nature, revealed that the HIV's capsid was a three-helix bundle with important molecular interactions at the capsid's seams. The seams are needed for the shell's stability and assembly and could represent vulnerabilities in the viral genome's protective coat.

"The capsid is very sensitive to mutation, so if we can disrupt those interfaces, we could interfere with capsid function," Zhang said. "The capsid has to remain intact to protect the HIV genome and get it into the human cell, but once inside it has to come apart to release its content so that the virus can replicate. Developing drugs that cause capsid dysfunction by preventing its assembly or disassembly might stop the virus from reproducing."

The project received funding from the National Science Foundation and the National Institutes of Health.

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