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!
Using DNA origami to build nanodevices of the future
31.08.2015 | Institute for Integrated Cell-Material Sciences at Kyoto University
An ounce of prevention: Research advances on 'scourge' of transplant wards
28.08.2015 | University of Wisconsin-Madison
China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from University of Arizona geoscientists. The study is the first to explain how the steep-fronted plateau formed.
China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from...
The leaves of the lotus flower, and other natural surfaces that repel water and dirt, have been the model for many types of engineered liquid-repelling surfaces. As slippery as these surfaces are, however, tiny water droplets still stick to them. Now, Penn State researchers have developed nano/micro-textured, highly slippery surfaces able to outperform these naturally inspired coatings, particularly when the water is a vapor or tiny droplets.
Enhancing the mobility of liquid droplets on rough surfaces could improve condensation heat transfer for power-plant heat exchangers, create more efficient...
Longer, more severe, and hotter droughts and a myriad of other threats, including diseases and more extensive and severe wildfires, are threatening to transform some of the world's temperate forests, a new study published in Science has found. Without informed management, some forests could convert to shrublands or grasslands within the coming decades.
"While we have been trying to manage for resilience of 20th century conditions, we realize now that we must prepare for transformations and attempt to ease...
A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.
The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...
A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).
Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...
20.08.2015 | Event News
20.08.2015 | Event News
19.08.2015 | Event News
02.09.2015 | Physics and Astronomy
02.09.2015 | Life Sciences
02.09.2015 | Awards Funding