New look at multi-talented protein sheds light on mysteries of HIV

New insights into the human immunodeficiency virus (HIV) infection process, which leads to acquired immunodeficiency syndrome (AIDS), may now be possible through a research method recently developed in part at the National Institute of Standards and Technology (NIST), where scientists have glimpsed an important protein molecule's behavior with unprecedented clarity.

The Gag protein is central to the assembly of new HIV virus particles. (a) Folded Gag molecules (multicolored) arise in the cellular cytoplasm. (b) Gag binds the viral RNA (black wavy lines) and drags it into the forming particle. (c) Gag molecules also may create assembly sites, where (d) Gag must stretch out to pack into the growing virus. (e) Virus particles eventually bud off from the host cell.

The HIV protein, known as Gag, plays several critical roles in the assembly of the human immunodeficiency virus in a host cell, but persistent difficulties with imaging Gag in a lab setting have stymied researchers' efforts to study how it functions.

"A better understanding of Gag's behavior might allow researchers to develop antiviral drugs that target the HIV assembly process, which remains unassailed by medical science," says Hirsh Nanda, a postdoctoral researcher at the NIST Center for Neutron Research (NCNR) and a member of the multi-institutional research team. "Our method might reveal how to inhibit new viruses as they grow."

The Gag molecule is a microscopic gymnast. At different stages during HIV assembly, the protein twists itself into several different shapes inside a host cell. One shape, or conformation, helps it to drag a piece of HIV genetic material toward the cell membrane, where the viral particles grow.

Gag's opposite end becomes anchored there, stretching the protein into a rod-like conformation that eventually helps form a barrier surrounding the infectious genes in the finished virus. But while scientists have been aware for years that Gag appears to play several roles in HIV assembly, the specifics have remained mysterious.