Only about 30 known human cases of hantavirus are reported in the US each year. The respiratory syndrome caused by a hantavirus infection comes from breathing in small viral particles in the excrement of infected rodents.
It starts out with flu-like symptoms that quickly deteriorate into a dangerous form of adult respiratory distress syndrome. It is among the most deadly known human viruses: 30 percent to 40 percent of people who are diagnosed die from hantavirus pulmonary fever.
A PLOS Pathogens paper by Penn microbiologists Paul Bates, PhD, and Kenneth Briley, PhD, published this month reports that four proteins key to cholesterol synthesis and uptake are highjacked by the hantavirus to enter human host cells. To identify host-cell genes needed for viral replication, Bates and Briley first used a less dangerous virus that was engineered to exhibit some characteristics of a member of the hantavirus group found in South America called Andes virus (ANDV). Although the molecular details are still being deciphered, it appears that adequate cellular cholesterol levels are needed to transport the virus into the cell.
This is not the first time that cholesterol-related proteins have been implicated in viral entry and infection but Bates says, "the hantaviruses seem to be exquisitely sensitive to the cellular cholesterol levels."
The four proteins identified by the Penn researchers are part of a protein complex that regulates cholesterol production in the cells of mammals. They found that treating cells that originated from human airways with an experimental drug that targets one of the four proteins made the cells less susceptible to infection. The experimental drug also lowers cholesterol levels in cells, so Bates wondered whether statins could be used to fight a hantavirus infection.
The researchers found that pre-treatment of human airway cells with a generic statin called mevastatin, which lowers cholesterol by a mechanism that does not involve the four proteins they identified, made the human airway cells less susceptible to ANDV infection. They tested both the experimental drug, PF-429242, and mevastatin, and both were effective against hantavirus, as measured by how many cells are infected with and without the drugs.
Bates surmises that statins might be given after a known hantavirus infection, or even prophylactically to exposed individuals.
Although the drug inhibition studies initially used the engineered virus, Bates used ANDV itself in high-containment Biosafety Level (BSL)-3 facilities in the Department of Microbiology at Penn to confirm that the results were true for ANDV as well. The next step is to test cholesterol-lowering drugs in an animal model for ANDV infection, working with collaborators to perform the animal studies in a BSL-4 at a national facility.
Karen Kreeger | EurekAlert!
Portable finger-probe device can successfully measure liver function in potential organ donors
29.05.2015 | University of California - Los Angeles Health Sciences
Project start: New active substance targeting dreaded hospital pathogens
29.05.2015 | Deutsches Zentrum für Infektionsforschung
Many joining and cutting processes are possible only with lasers. New technologies make it possible to manufacture metal components with hollow structures that are significantly lighter and yet just as stable as solid components. In addition, lasers can be used to combine various lightweight construction materials and steels with each other. The Fraunhofer Institute for Laser Technology ILT in Aachen is presenting a range of such solutions at the LASER World of Photonics trade fair from June 22 to 25, 2015 in Munich, Germany, (Hall A3, Stand 121).
Lightweight construction materials are popular: aluminum is used in the bodywork of cars, for example, and aircraft fuselages already consist in large part of...
Using ultrashort laser pulses, scientists in Max Planck Institute of Quantum Optics have demonstrated the emission of extreme ultraviolet radiation from thin dielectric films and have investigated the underlying mechanisms.
In 1961, only shortly after the invention of the first laser, scientists exposed silicon dioxide crystals (also known as quartz) to an intense ruby laser to...
The only professorship in Germany to date, one master's programme, one laboratory with worldwide unique equipment and the corresponding research results: The University of Würzburg is leading in the field of biofabrication.
Paul Dalton is presently the only professor of biofabrication in Germany. About a year ago, the Australian researcher relocated to the Würzburg department for...
Physicists have developed an innovative method that could enable the efficient use of nanocomponents in electronic circuits. To achieve this, they have developed a layout in which a nanocomponent is connected to two electrical conductors, which uncouple the electrical signal in a highly efficient manner. The scientists at the Department of Physics and the Swiss Nanoscience Institute at the University of Basel have published their results in the scientific journal “Nature Communications” together with their colleagues from ETH Zurich.
Electronic components are becoming smaller and smaller. Components measuring just a few nanometers – the size of around ten atoms – are already being produced...
Development and implementation of an advanced automobile parking navigation platform for parking services
To fulfill the requirements of the industry, PolyU researchers developed the Advanced Automobile Parking Navigation Platform, which includes smart devices,...
20.05.2015 | Event News
18.05.2015 | Event News
12.05.2015 | Event News
29.05.2015 | Life Sciences
29.05.2015 | Earth Sciences
29.05.2015 | Physics and Astronomy