Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Shutting down the HIV assembly line

11.03.2005


After infecting a susceptible cell, the human immunodeficiency virus hijacks that cell’s normal machinery to produce carbon copies of itself. New HIV particles roll off the cellular assembly lines, burst like bubbles out of the cell, and float off to invade other cellular factories. Vanderbilt University Medical Center investigators have now identified an early step in HIV particle assembly. The findings, published March 11 in Cell, could lead to new drugs that combat HIV infection by shutting down the virus’s assembly lines.



For several years, Paul W. Spearman, M.D., associate professor of Pediatrics and Microbiology & Immunology, and colleagues have been studying the assembly of HIV particles, specifically the distinct steps HIV structural proteins take in order to come together and create a viral particle. "The assembly process is just one part of the whole HIV life cycle," Spearman noted, "but it’s an important part in that each step along the way is required to make an infectious viral particle."

Spearman’s team has focused on a protein called "Gag," the major HIV structural protein. In recent years, Spearman said, it has become apparent that Gag moves to a compartment in the cell called the multivesicular body, or late endosome. In some cell types, Gag and the HIV viral envelope protein form particles in the multivesicular body; in other cell types, Gag makes its way from this site to the cell membrane before assembling into particles.


Although many studies have demonstrated that Gag is present in the late endosome and have focused on particle assembly at that point, none have tackled how the Gag protein gets there in the first place. The current work fills this gap. Spearman and colleagues used the HIV-1 Gag protein as bait to "fish" for Gag binding partners. They identified several known and novel interacting proteins and selected one, the delta subunit of AP-3, for further evaluation. AP-3 is an "adaptor protein complex," a group of four proteins known to sort cargo proteins to specific compartments in the cell.

Through a series of experiments, the group demonstrated that the AP-3 delta subunit interacts with Gag to direct it to the multivesicular body. Disruption of the interaction, using a specific piece of the AP-3 subunit, eliminated Gag trafficking to the multivesicular body and diminished HIV particle formation in cells. "The significance of this paper comes from really identifying how Gag gets to the multivesicular body and in demonstrating that if you block that trafficking step specifically, you block production of particles," Spearman said. "That says this is not a dead-end pathway, but that it is part of the normal, productive assembly pathway."

The newly identified early step in the HIV assembly process could be a target for a new generation of drugs to combat the virus. No existing anti-HIV drugs disrupt particle assembly or the movement of Gag in the cell. "We have hopes of identifying compounds that inhibit this Gag-AP-3 interaction and that may lead to new efforts to treat HIV infection," Spearman said.

Such drugs should be very specific, he said, since it should be possible to block Gag’s interaction with AP-3 without disrupting AP-3 function in the cell. And by targeting an early step in HIV particle assembly, an inhibitor of this sort would be expected to block viral replication in cells that complete assembly at the multivesicular body as well as those that assemble particles at the cell membrane.

Leigh MacMillan | EurekAlert!
Further information:
http://www.vanderbilt.edu

More articles from Health and Medicine:

nachricht Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Foods of the future
15.08.2018 | Georg-August-Universität Göttingen

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>