Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hoping for a fluorescent basket case

16.11.2009
How HIV is assembled and released from infected cells

Although recent advances have raised hopes that a protective vaccine can be developed, acquired immunodeficiency syndrome (AIDS) remains a major public health problem. Much has been learned about HIV-1, the virus that causes the disease.

However, basic aspects of person-to-person transmission and of the progressive intercellular infection that depletes the immune system of its vital T cells remain imperfectly understood. In a paper published today in the online journal PloS Pathogens, Professor Don Lamb's group at the Ludwig-Maximilians-Universitaet (LMU) in Munichs's Department of Chemistry and Biochemistry, together with colleagues in Heidelberg, describe in detail how new virus particles assemble at the membrane of infected cells, and are released to attack healthy cells nearby. The new findings could help provide clues as how to interrupt the process of intercellular viral spread. (PLoS Pathogens, 6 November 2009)

As many of us have learned from personal experience, computer viruses, which contain short pieces of malicious code and arrive in anonymous packages, can gum up data-processing routines. This definition also fits their biological counterparts, which generally comprise compact genomes packed in protein shells, and enter cells via specific portals. For example, the retrovirus HIV-1 has only nine genes in its RNA genome and infects cells by binding to specific receptors. Inside the cell, the genetic material is copied and 15 viral proteins are synthesized. They interact to pack the genomic RNA into new viral particles. These are then extruded from the cell, wrapped in an envelope of membrane bearing viral proteins that direct the parcel to the next susceptible cell.

The basket that encases the viral RNA is constructed from the Gag protein. Gag is highly versatile: It can bind to the inner face of the cell membrane, to the viral RNA, to itself (to form the shell around the RNA) and to cellular proteins that extrude the newly assembled particle into the extracellular medium. Indeed, Gag can form virus-like particles in the absence of other viral proteins. For their experiments, Professor Lamb's team used cultured cells containing eight of the HIV-1 genes, one of which coded for a fluorescent form of Gag.

"We adopted our custom-built microscope specifically for the experiment, visualizing Gag in the cellular plasma membrane by Total Internal Reflection Fluorescence Microscopy while alternately switching to Wide-Field Fluorescence Microscopy to get a deeper view into the cell", explains Lamb. This allowed the team to track single Gag particles and follow the assembly process, in real time.

Once virus assembly is switched on within an infected cell, the membrane surface of the cell becomes covered with viruses in one to two hours. Each virus is assembled individually at the plasma membrane on the time scale of minutes, rejecting the idea of a reusable assembly platform that is believed to exist for other viruses. By tracking individual viruses, the scientist could follow the processes of assembly from initiation of assembly through to release, learning that it takes about 25 minutes to produce an HIV virus. Hence, a lag of 15-20 minutes precedes release of the enveloped virus, presumably because it takes time for the hijacked cellular budding machinery to close of the virus and release it into to the extracellular medium.

"Using a 'photoconvertible' version of the famous green fluorescent protein – whose discovery and utilization in biological systems were honored with the Nobel prize in chemistry in 2008 – attached to the Gag protein, we were able to convert the color of membrane bound Gag proteins from green to red", says Lamb. "Thereby, we could determine that viruses were assembly from protein delivered directly from the cytosol or had only arrived recently to the plasma membrane." The new findings add an important dynamic dimension to the process of intercellular viral spread. If they help find ways to interrupt it, HIV-1 could finally be stamped as "undeliverable". (PH)

Publication:
"Dynamics of HIV-1 assembly and release"
Sergey Ivanchenko, William J. Godinez, M. Lampe, H.G. Kräusslich, R. Eils, K. Rohr, C. Bräuchle, B. Müller, D.C. Lamb

PLoS Pathogens, 6 November 2009

Contact:
Professor Dr. Don C. Lamb
Department of Chemistry and Biochemistry
Excellence clusters "Nanosystems Initiative Munich" (NIM) and "Center for Integrated Protein Science Munich" (CiPSM) at LMU Munich
Tel.: +49 (0) 89 / 2180 - 77564
E-mail: Don.Lamb@cup.uni-muenchen.de

Dr. Don C. Lamb | EurekAlert!
Further information:
http://www.uni-muenchen.de

More articles from Life Sciences:

nachricht Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie

nachricht Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Molecular Force Sensors

20.09.2017 | Life Sciences

Producing electricity during flight

20.09.2017 | Power and Electrical Engineering

Tiny lasers from a gallery of whispers

20.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>