National Institutes of Health (NIH) scientists have found that Middle East respiratory syndrome coronavirus (MERS-CoV) infection in marmosets closely mimics the severe pneumonia experienced by people infected with MERS-CoV, giving scientists the best animal model yet for testing potential treatments.
Researchers at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) used marmosets after predicting in computer models that the animals could be infected with MERS-CoV based on the binding properties of the virus.
Rather than randomly testing animal species that might provide a better model by infecting them with MERS-CoV, researchers led by Heinz Feldmann and Vincent Munster (both from Rocky Mountain Laboratories in Hamilton, Mont.) 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 human proteins are located away from the part of DPP4 that binds the viral spike protein.
The same NIAID group in December 2012 developed the first animal model of MERS-CoV infection using rhesus macaques. That model has proven difficult to use for evaluating potential treatments because it mimics mild to moderate human disease, and the animals quickly recover from infection.
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.
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.”
The MERS outbreak, which began in 2012, continues throughout the Middle East. Since the outbreak began, NIAID researchers have focused on understanding how the virus causes disease and how it can be treated effectively.
As of July 23rd, the World Health Organization has reported a total of 837 human cases of MERS-CoV infection, including at least 291 deaths.
PLoS Pathogens: MERS-CoV Causes Lethal Pneumonia in the Common Marmoset