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 Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht Identified the component that allows a lethal bacteria to spread resistance to antibiotics
27.07.2017 | Institute for Research in Biomedicine (IRB Barcelona)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Physicists Design Ultrafocused Pulses

Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.

Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

Programming cells with computer-like logic

27.07.2017 | Life Sciences

Identified the component that allows a lethal bacteria to spread resistance to antibiotics

27.07.2017 | Life Sciences

Malaria Already Endemic in the Mediterranean by the Roman Period

27.07.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>