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!
Antibiotic effectiveness imperiled as use in livestock expected to increase
27.03.2015 | Princeton University
A human respiratory tissue model to assess the toxicity of inhaled chemicals and pollutants
26.03.2015 | R&D at British American Tobacco
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
27.03.2015 | Agricultural and Forestry Science
27.03.2015 | Materials Sciences
27.03.2015 | Ecology, The Environment and Conservation