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!
Live probiotics can re-balance the gut microbiome and modify immune system response
20.11.2018 | Symprove
Purdue cancer identity technology makes it easier to find a tumor's 'address'
16.11.2018 | Purdue University
Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.
Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
20.11.2018 | Life Sciences
20.11.2018 | Life Sciences
20.11.2018 | Physics and Astronomy