New look at multitalented protein sheds light on mysteries of HIV

October 14, 2010
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. Credit: NIST

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, where scientists have glimpsed an important protein molecule's behavior with unprecedented clarity.

The , known as Gag, plays several critical roles in the assembly of the 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 that target the 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 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.

The research team potentially solved this problem by creating an artificial cell membrane where Gag can show off its gymnastic prowess for the neutron probes at the NCNR. The center includes a variety of instruments specifically designed to observe large like proteins.

"We were able to mimic the different stages of the virus's development, and look at what Gag's conformation was at these various stages," Nanda says. "We saw conformations that had never been seen before."

Nanda describes the team's first paper* on the subject as an important first step in describing their observational method, which was a joint effort between NIST, the National Cancer Institute and Carnegie-Mellon University. They plan another paper detailing what the method has revealed about HIV.

"Our efforts have not yet shown us how many steps are involved in Gag's work assembling an HIV particle, but at least we can see what it looks like in each major interaction that likely occurs in the cell during assembly," Nanda says. "It may allow us to characterize them for the first time."

Nanda says that their technique will also allow scientists to examine large classes of membrane proteins, which like Gag are notoriously hard to examine.

Explore further: Effective HIV control may depend on viral protein targeted by immune cells

More information: *H. Nanda, S.A.K. Datta, F. Heinrich, M. Lösche, A. Rein, S. Krueger, J.E. Curtis. Electrostatic interactions and binding orientation of HIV-1 matrix, studied by neutron reflectivity. Biophysical Journal, Vol. 99 (8), Oct. 20, 2010.

Related Stories

How sneaky HIV escapes cells

June 5, 2007

Like hobos on a train, HIV, the virus that causes AIDS, uses a pre-existing transport system to leave one infected cell and infect new ones, Hopkins scientists have discovered. Their findings, published in the June issue ...

New electron microscopy images reveal the assembly of HIV

June 23, 2009

Scientists at the European Molecular Biology Laboratory (EMBL) and the University Clinic Heidelberg, Germany, have produced a three-dimensional reconstruction of HIV (Human Immunodeficiency Virus), which shows the structure ...

Imaging study shows HIV particles assembling around its genome

November 17, 2009

( -- The genesis of one the planet's most lethal viruses, HIV, has been caught on tape. New imaging experiments show individual HIV genomes -- strands of RNA — docking on the inner membrane of an infected cell ...

Retrovirus replication process different than thought

July 15, 2010

How a retrovirus, like HIV, reproduces and assembles new viruses is different than previously thought, according to Penn State College of Medicine researchers. Understanding the steps a virus takes for assembly could allow ...

Recommended for you

New approach for 'nanohoops' could energize future devices

October 12, 2015

When Ramesh Jasti began making tiny organic circular structures using carbon atoms, the idea was to improve carbon nanotubes being developed for use in electronics or optical devices. He quickly realized, however, that his ...

The universe's most miraculous molecule

October 9, 2015

It's the second most abundant substance in the universe. It dissolves more materials than any other solvent. It stores incredible amounts of energy. Life as we know it would not be possible without it. And although it covers ...

Trio wins Nobel Prize for mapping how cells fix DNA damage

October 7, 2015

Tomas Lindahl was eating his breakfast in England on Wednesday when the call came—ostensibly, from the Royal Swedish Academy of Sciences. It occurred to him that this might be a hoax, but then the caller started speaking ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.