Scientists report that they have developed a mouse model for MERS-CoV infection, possibly opening the way to test potential MERS drugs and vaccines in mice.
Mice and other small lab animals are not susceptible to MERS-CoV, and experimental infection has been demonstrated only in macaques, the authors said in a report published yesterday in the Proceedings of the National Academy of Sciences (PNAS). The scientists are from several US universities and a research center in Madrid.
The team modified an adenovirus to express the human host-cell receptor for MERS-CoV, dipeptidyl peptidase 4. After they inoculated mice intranasally with this virus, it sensitized them to MERS-CoV. Mice infected with MERS-CoV became ill with pneumonia involving extensive inflammation, but they were able to clear the virus within 6 to 8 days. Mice with normal immune systems had mild disease, whereas immunocompromised mice were more severely affected.
In further steps, the team determined that a toll-like receptor agonist called poly I:C showed promise as a MERS treatment in mice. They also found that a Venezuelan equine encephalitis virus engineered to express the MERS-CoV spike protein might have potential as a vaccine.
The authors say it took only 2 to 3 weeks to develop the mouse model using the engineered adenovirus, whereas it can take months to years to develop transgenic mice that express a human receptor.
"Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections," they assert.