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:
PLoS Pathogens, 6 November 2009Contact:
Dr. Don C. Lamb | EurekAlert!
Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology
Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences