Friday, 18 March 2016

Back to the bats for MERS-CoV...

It's a smoking bat. Get it? Hmm.
In late February Munster and a team of United States' researchers infected bats with MERS-CoV. 

The aim here was to seek out information about a possible origin for MERS-CoV in bats and perhaps find an animal source from which camels may have first been infected. This path is suspected because of the genetic similarities between MERS-CoV and other bat coronaviruses which make bats an attractive reservoir for MERS-CoV...or an earlier form of MERS-CoV.

It's worth reinforcing that there is as yet no "smoking bat" - no bat species has been found to harbour infectious MERS-CoV in the wild or more than a diagnostic PCR fragment's worth of genetic material. To date.

The team used a bat species called Artibeus jamaicensis - the Jamaican fruit bat. 

They first tested whether the bat's version of the molecular known to be the human MERS-CoV receptor,  dipeptidyl peptidase 4 (DPP4), could act in that role. To do this they cloned the relevant bat sequence and introduced it into some some cells that usually didn't permit MERS-CoV to infect and replicate wihtin them. When the introduced DPP4 material was expressed, the cells permitted MERS-CoV infection and replication; Jamaican fruit bat DPP4 could act as the MERS-CoV receptor, just like human DPP4 does.

From the Histology Lecture Image Gallery at Yale
Medical Cell Biology.[3]
Next the team infected 10 A.jamaicensis bats via the nose and body cavity; none showed signs of disease, lost weight or were found to have a rise in their temperature but 8 shed virus - moreso from their respiratory than their gastrointestinal tracts.

When the bats were killed at different times and examined, the lower respiratory tract was found to contain the highest level of virus, but MERS-CoV was also found throughout the bodies of the bats, possibly spread via a blood-borne path since viral RNA was detected in the blood 2 and 4 days after inoculation. 

Signs of mild tissue damage could only be found in 2 bats - both in the respiratory tract with signs that virus infected Type I pneumocytes. Type I pneumocytes form part of the alveolar gas exchange barrier. In humans, Type II pneumocytes were identified as MERS-CoV targets in the only human autopsy conducted to date.[2] Type II pneumocytes are responsible for secreting surfactant which helps stop the lung's air sacs from sticking to themselves, they metabolize drugs, move water across epithelium (tissues that line the body's hollow cavities in this case) and repair injured alveoli.[4]

Only 1 bat developed a MERS-CV a specific antibody response.

The discussion had some interesting points including....
  • A.jamaicensis may be a good model system for studies of how bats and their coronaviruses co-exist
  • MERS-CoV "maintains the ability to efficiently replicate" in bats which the authors take to support the hypothesis that bats are the ancestral reservoir for MERS-CoV. Or maybe its ancestor?
  • Because bat coronaviruses are usually bat gut pathogens, but MERS-CoV was a bat respiratory pathogen, this might suggest MERS-CoV evolved to be so in camels. Orrrr...it might not.
  • In the absence of disease, a detectable antibody response may not occur in humans as was found in bats, or it may be delayed in humans as has been previously reported. 
  • In most bats and bat tissues, MERS-CoV RNA could not be detected beyond a 2 week period after inoculation - but in 1 bat, the small intestine was still positive at day 28

I'll get back onto the camel literature reviews next.

References...
  1. Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis)
    http://www.nature.com/articles/srep21878
  2. Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014
    http://ajp.amjpathol.org/article/S0002-9440(15)00647-1/abstract
  3. http://medcell.med.yale.edu/medcell.php#
  4. http://www.ncbi.nlm.nih.gov/pubmed/3285521