Statins may have use against killer virus

Date: Feb-12-2014New research suggests cholesterol-busting statins may be effective in

fighting the mysterious hantavirus, which can cause a potentially fatal respiratory

syndrome.

Microbiologists from the Perelman School of Medicine at the University of Pennsylvania (UPenn) have found that in order to gain entry into host cells, the virus hijacks proteins

that help regulate cholesterol, and statins could be a way to stop it being able to do that.

They report their findings in the open access journal PLOS Pathogens.

Hantavirus emerged suddenly in the US over 40 years ago and around 30 cases of human

infection are reported every year. The most recent well-known cluster of hantavirus infection was in Yosemite

National Park in 2012.

Humans can become infected with hantavirus through contact with infected rodents or their

urine and droppings.

Once infection sets in, flu-like symptoms develop that quickly deteriorate into a dangerous

form of adult respiratory distress syndrome. About 30-40% of people diagnosed with hantavirus

die of pulmonary fever.

In order to thrive, just like any other virus, hantavirus particles have to enter host cells,

where they hijack their protein-making machinery to make copies of themselves, which are then

released to infect more cells.

Hantavirus needs cholesterol to gain entry to host cell

In their study paper, the Penn researchers describe how they started their investigation of

hantavirus by looking for aspects of human cells that might be important for viral

infection.

To do this, they did most of their experiments using less dangerous viruses genetically

engineered to share characteristics of a hantavirus group known as the Andes virus (ANDV). They

then used ANDV itself to confirm results.

Although they are still working out some of the molecular details, the researchers say it

looks like hantavirus needs cholesterol to help it get into cells.

This is not the first time that researchers have shown viruses using cholesterol in this way,

but in the case of hantaviruses, it appears they are "exquisitely sensitive to the cellular

cholesterol levels," says Dr. Paul Bates, who heads a UPenn lab that studies host-virus

interactions.

Using two independent genetic methods, the team identified four proteins that are part of a

complex that regulates cholesterol production in mammalian cells.

Drug and statin made airway cells less susceptible to hantavirus infection

They found an experimental drug - called PF-429242 that targets one of these proteins - when

used to treat cells from human airways, made them less vulnerable to infection by hantavirus.

The drug also lowered levels of cholesterol in the cells.

This made them wonder if existing cholesterol-busters like statins might have a similar

effect. Could they be used to fight a hantavirus infection?

They ran further tests using the generic drug mevastatin. This lowers cholesterol by a

mechanism that does not involve the four proteins they identified.

The results showed that pre-treatment with mevastatin made the human airway cells less

susceptible to hantavirus.

Then in a final experiment, they found pre-treatment with both the experimental drug and the

statin was effective against hantavirus, as measured by comparing the number of cells infected

with and without pre-treatment.

The researchers conclude hantavirus appears to be sensitive to changes in cholesterol levels

and perhaps approved drugs that target cholesterol production already offer a way of fighting

infection by this deadly virus.

They suggest the next step should be to test cholesterol-lowering drugs in animals

infected with ANDV, in a national lab with a higher level of biosecurity.

Written by Catharine Paddock PhD




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