Now, UTMB researchers have uncovered what they believe could be the major factor contributing to the SARS virus' virulence: the pathogen's use of a single viral protein to weaken host cell defenses by launching a "two-pronged" attack on cellular protein-synthesis machinery.
Their results show that copies of this viral protein, known as nsp1, directly interferes with the tiny cellular machines called ribosomes, which make the proteins, such as interferon beta, that are crucial for immune defense. (If the word "ribosome" sounds familiar, it's probably because the three scientists who first determined what the miniature protein factories look like and how they function won the 2009 Nobel Prize for Chemistry.) Nsp1 is also involved in degrading the biochemical messages that are decoded by these ribosomes to produce such proteins.
"This SARS virus protein, nsp1, binds to ribosomes to inactivate them and also modifies messenger RNA molecules to make them unreadable," said UTMB professor Shinji Makino, senior author of a paper on the discovery appearing in the online edition of Nature Structure and Molecular Biology. "We think that this property of nsp1 could be a major player in the virulence of SARS."
Makino and the article's other authors — postdoctoral fellows Wataru Kamitani, Cheng Huang and Kumari Lokugamage, and senior research scientist Krishna Narayanan — identified nsp1's dual effect with a series of experiments mainly done using purified nsp1 protein in a special "cell-free" system. This widely used test-tube platform, known as a "rabbit reticulocyte lysate" (RRL) system, contained only the subcellular structures and materials (ribosomes, amino acids and various control factors) that cells use to produce or "translate" proteins from messenger-RNA templates.
The researchers also developed a mutant form of the nsp1 protein that was incapable of interfering with RNA translation, employing it as an experimental control.
By measuring the outcomes produced by mixing a variety of different messenger-RNA templates with either nsp1 or mutant nsp1 in RRL, the investigators generated a strikingly detailed picture of how nsp1 interferes with ribosomes and degrades messenger RNA. Nsp1 grabs on to ribosomes, attaching to a specific part known as the 40s subunit to shut down protein production Meanwhile, the messenger RNA molecules being translated into proteins on these ribosomes are degraded by processes tied to nsp1.
"This is interesting in part because it's a new mechanism — no other known protein uses this strategy," Makino said. "But there are more practical reasons why it's important to understand viral virulence factors, particularly when you consider the potential need for treatments. There are viruses similar to SARS circulating in China, and we have no way of knowing whether this virus may come back."
The U.S. Public Health Service and the James W. McLaughlin Foundation supported this work.
UTMB was established in 1891. The 84-acre campus includes four schools, three institutes for advanced study, a major medical library, a network of hospitals and clinics that provide a full range of primary and specialized medical care and numerous research facilities. UTMB is a component of the University of Texas System.
Jim Kelly | EurekAlert!
Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex
New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center
Russian researchers together with their French colleagues discovered that a genuine feature of superconductors -- quantum Abrikosov vortices of supercurrent -- can also exist in an ordinary nonsuperconducting metal put into contact with a superconductor. The observation of these vortices provides direct evidence of induced quantum coherence. The pioneering experimental observation was supported by a first-ever numerical model that describes the induced vortices in finer detail.
These fundamental results, published in the journal Nature Communications, enable a better understanding and description of the processes occurring at the...
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
25.06.2018 | Physics and Astronomy
25.06.2018 | Earth Sciences
25.06.2018 | Power and Electrical Engineering