The marmoset animal model recapitulates disease symptoms of MERS infection in humans

August 21, 2014
MERS-CoV particles (yellow) attach to camel tissue cells. Credit: NIAID

An article published on August 21st in PLOS Pathogens reports the first animal model that recapitulates the severe and sometimes lethal respiratory symptoms seen in human patients and suggests that the common marmoset will play an important role in the development effective countermeasures against Middle East respiratory syndrome corona virus.

Recent studies had identified how the MERS-CoV recognizes and invades : its spike protein binds to DPP4, a protein on the surface of human cells, and this leads to internalization of the which then takes over the human cell and turns it into a virus factory. Variations in DPP4 between seem to determine susceptibility to MERS-CoV infection. For example, mice, hamsters, or ferrets, whose DPP4 is quite different from the , seem resistant to the virus while rhesus macaques, whose DPP4 is very similar to the human one, are susceptible. However, while they can be infected with MERS-CoV, they develop only mild-to-moderate symptoms, unlike many human patients that carry very high loads of virus, get seriously ill, and sometimes die.

Rather than randomly testing animal species that might provide a better by infecting them with MERS-CoV, researchers led by Heinz Feldmann and Vincent Munster (both from Rocky Mountain Laboratories, part of the U.S. National Institute of Allergy and Infectious Diseases in Hamilton, Mont., USA) set out to identify animals whose DPP4 protein was similar to humans, especially the part known to bind directly to the viral spike protein. They found that marmoset DPP4 has an identical amino-acid sequence (amino acids are building blocks of proteins) to human DPP4 in the critical region. A three-dimensional model confirmed that any DPP4 amino acids that differed between the marmoset and proteins are located away from the part of DPP4 that binds the viral spike protein.

Having thus good reasons to believe that marmosets would be susceptible to MERS-CoV infection, the researchers went on to infect nine animals with the virus. All of them got sick, and their lungs contained high loads of virus and showed signs of immune response and inflammation. Most animals developed progressive severe pneumonia, and two animals had to be euthanized according to pre-determined guidelines, because their condition worsened dramatically.

While this is an initial report and the researchers point to the need for additional experiments, they see several advantages of the marmoset over the rhesus macaque model and expect that "marmosets will serve as the animal of choice for future therapeutic studies where possible." They also state that "the development of the more severe marmoset model will ensure a better pre-clinical analysis of treatments prior to clinical trials in humans" and express the hope that their model will make "a significant contribution to reducing the impact of MERS-CoV on global public health."

Explore further: Team finds potential MERS transmission mechanism between bats and humans

More information: Falzarano D, de Wit E, Feldmann F, Rasmussen AL, Okumura A, et al. (2014) Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset. PLoS Pathog 10(8): e1004250. DOI: 10.1371/journal.ppat.1004250

N van Doremalen et al. Host species restriction of Middle East respiratory syndrome coronavirus through its receptor dipeptidyl peptidase 4. Journal of Virology DOI: 10.1128/JVI.00676-14 (2014).

Related Stories

Team finds potential MERS transmission mechanism between bats and humans

August 12, 2014
Researchers have identified the mechanism used by the deadly MERS virus to transmit from bats to humans. Bats are a native reservoir for MERS and the finding could be critical for understanding the animal origins of the virus, ...

Origin of MERS coronavirus identified

October 10, 2013
The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has circulated in bats for a substantial time, before making the species leap to humans, according to research published in BioMed Central's open access ...

Scientists identify antibodies against MERS

April 28, 2014
Scientists at Dana-Farber Cancer Institute have identified natural human antibodies against the virus that causes Middle East Respiratory Syndrome (MERS), a step toward developing treatments for the newly emerging and often-fatal ...

New experimental vaccine produces immune response against MERS virus

April 30, 2014
The University of Maryland School of Medicine (UM SOM) and Novavax, Inc. today announced that an investigational vaccine candidate developed by Novavax against the recently emerged Middle East Respiratory Syndrome Coronavirus ...

Middle East Respiratory Syndrome coronavirus detected in the air of a Saudi Arabian camel barn

July 22, 2014
Saudi Arabian researchers have detected genetic fragments of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in the air of a barn holding a camel infected with the virus. The work, published this week in mBio, the ...

Signs of MERS coronavirus found in dromedary camels

August 8, 2013
Researchers searching for signs of Middle East respiratory syndrome coronavirus (MERS-CoV) in livestock animals have found antibodies specific to the new virus in dromedary camels. The research, published in The Lancet Infectious ...

Recommended for you

Phase 3 trial confirms superiority of tocilizumab to steroids for giant cell arteritis

July 26, 2017
A phase 3 clinical trial has confirmed that regular treatment with tocilizumab, an inhibitor of interleukin-6, successfully reduced both symptoms of and the need for high-dose steroid treatment for giant cell arteritis, the ...

A large-scale 'germ trap' solution for hospitals

July 26, 2017
When an infectious airborne illness strikes, some hospitals use negative pressure rooms to isolate and treat patients. These rooms use ventilation controls to keep germ-filled air contained rather than letting it circulate ...

Researchers report new system to study chronic hepatitis B

July 25, 2017
Scientists from Princeton University's Department of Molecular Biology have successfully tested a cell-culture system that will allow researchers to perform laboratory-based studies of long-term hepatitis B virus (HBV) infections. ...

Male hepatitis B patients suffer worse liver ailments, regardless of lifestyle

July 25, 2017
Why men with hepatitis B remain more than twice as likely to develop severe liver disease than women remains a mystery, even after a study led by a recent Drexel University graduate took lifestyle choices and environments ...

Mind-body therapies immediately reduce unmanageable pain in hospital patients

July 25, 2017
Mindfulness training and hypnotic suggestion significantly reduced acute pain experienced by hospital patients, according to a new study published in the Journal of General Internal Medicine.

Research examines lung cell turnover as risk factor and target for treatment of influenza pneumonia

July 24, 2017
Influenza is a recurring global health threat that, according to the World Health Organization, is responsible for as many as 500,000 deaths every year, most due to influenza pneumonia, or viral pneumonia. Infection with ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.