Photo Credit Wikipedia
# 7805
Two weeks ago, in Nature: Animal Testing Of Drug Combo Shows Potential For Treating MERS, we looked at the the potential role of Interferon-α2b & ribavirin in the treatment of MERS-CoV infection, based on a NIAID led study conducted on rhesus macaques. At the time I cautioned that, while encouraging, the following caveats should be kept in mind:
- First, the macaque model is not a perfect substitute for humans, as they tend not to be as severely impacted by the MERS virus.
- Second, treatment was initiated 8 hours post infection, which is an earlier pharmacological intervention than most humans could hope to see.
- And third, most severe human infections have been seen in people with co-morbidities like COPD, cancer, diabetes, asthma . . . variables this study does not attempt to replicate.
These same group of researchers are back with a another study - published yesterday in the journal PNAS - that looks at the pathogenesis of MERS-CoV in rhesus macaques. Once again, caveats 1 and 3 need to be considered.
The study is called:
Emmie de Wita, Angela L. Rasmussenb, Darryl Falzaranoa, Trenton Bushmakera, Friederike Feldmannc, Douglas L. Briningc, Elizabeth R. Fischerd, Cynthia Martellaroa, Atsushi Okumurab, Jean Changb, Dana Scottc, Arndt G. Beneckeb,e, Michael G. Katzeb, Heinz Feldmanna,f,1, and Vincent J. Munstera,1
Significance
The Middle East respiratory syndrome coronavirus (MERS-CoV) is the latest emerged coronavirus causing severe respiratory disease with a high case fatality rate in humans. To better understand the disease caused by MERS-CoV, we developed a rhesus macaque model. Infection of rhesus macaques with MERS-CoV resulted in the rapid development of a transient pneumonia, with MERS-CoV replication largely restricted to the lower respiratory tract. This affinity of MERS-CoV for the lungs partly explains the severity of the disease observed in humans. The MERS-CoV rhesus macaque model will be instrumental in developing and testing vaccine and treatment options for an emerging viral pathogen with pandemic potential.
Abstract
(Excerpt)
Upon a combination of intratracheal, ocular, oral, and intranasal inoculation with 7 × 106 50% tissue culture infectious dose of the MERS-CoV isolate HCoV-EMC/2012, rhesus macaques developed a transient lower respiratory tract infection. Clinical signs, virus shedding, virus replication in respiratory tissues, gene expression, and cytokine and chemokine profiles peaked early in infection and decreased over time. MERS-CoV caused a multifocal, mild to marked interstitial pneumonia, with virus replication occurring mainly in alveolar pneumocytes. This tropism of MERS-CoV for the lower respiratory tract may explain the severity of the disease observed in humans and the, up to now, limited human-to-human transmission.
In simple language, once infected, macaques developed mild to moderate, albeit short-lived pneumonia, with infection and viral replication most prominently seen in the lower lung tissue. This tropism (affinity) of the virus for the lower respiratory tract in macaques does match what we’ve seen in severe human cases, but in macaques the severity and duration of MERS infection was limited.
We lack a fully predictive animal model for human medical research. Mice, guinea pigs, and ferrets are often employed because of their small size, low cost, and ease of use. Rhesus macaques, on the other hand, are more difficult to obtain and to work with, but are viewed as being a closer human analog.
Still, results with these animals must be accepted with a certain degree of caution. The old saying in biomedical research is that `Mice lie, and monkeys exaggerate.’
We’ve seen mild MERS infections in humans, primarily in younger patients and those without co-morbidities, and so it may well be that the young, healthy macaques used in this study are mirroring that cohort.
What this study does tell us is that this virus prefers the lower respiratory tract (in macaques), and that that may help explain both its severity in humans, and its limited human-to-human transmission to date.
For more on this story, Robert Roos of CIDRAP NEWS wrote an excellent overview last night.
Macaque study: MERS-CoV settles deep in lungs
Robert Roos | News Editor | CIDRAP News
Sep 23, 2013
Researchers say the macaque model will be useful in developing and testing vaccines and treatments for MERS.
If rhesus macaques are good stand-ins for humans in studying Middle East respiratory syndrome coronavirus (MERS-CoV), the virus prefers the environment deep in the lungs, a finding that may help explain some features of the disease in humans, according to new research.
The scientists say that in macaques, the virus mainly affects the lower respiratory tract, which may help explain why the human disease is often severe but does not spread very easily from person to person.
