virology blog
About viruses and viral disease
On episode #258 of the science show This Week in Virology, Matt joins the TWiV team to discuss the discovery of a SARS-like coronavirus in bats that can infect human cells, and what is going on with MERS-coronavirus.
You can find TWiV #258 at www.microbe.tv/twiv.
The SARS pandemic of 2002-2003 is believed to have been caused by a bat coronavirus (CoV) that first infected a civet and then was passed on to humans. The isolation of a new SARS-like coronavirus from bats suggests that the virus could have directly infected humans.
A single colony of horseshoe bats (Rhinolophus sinicus) in Kunming, Yunnan Province, China, was sampled for CoV sequences over a one year period. Of a total of 117 anal swabs or fecal samples collected, 27 (23%) were positive for CoV sequences by polymerase chain reaction (PCR). Seven different SARS-like CoV sequences were identified, including two new ones. For the latter the complete genome sequence was determined, which showed a higher nucleotide sequence identity (95%) with SARS-CoV than had been previously observed before among bat viruses.
One of these new viruses was recovered by infecting monkey cell cultures with one of the PCR-positive samples. This virus could infect human cells and could utilize human angiotensin converting enzyme 2 (ACE2) as an entry receptor. The infectivity of this virus could also be neutralized with sera collected from seven different SARS patients.
None of the SARS-like coronaviruses previously isolated from bats are able to infect human cells. The reason for this block in replication is that the spike glycoprotein of these bat viruses do not recognize ACE2, the cell receptor for SARS-CoV. SARs-like CoVs isolated from palm civets during the 2002-2003 outbreak have amino acid changes in the viral spike glycoprotein that improve its interaction with ACE2. The civet was therefore believed to be an intermediate host for adaptation of SARS-CoV to humans. The isolation of bat SARS-like CoVs that can bind human ACE2 and replicate in human cells suggests that the virus might have spread directly from bats to humans.
This finding has implications for public health: if SARS-like CoVs that can infect human cells are currently circulating in bats, they have the potential to infect humans and cause another outbreak of disease. The authors believe that the diversity of bat CoVs is higher than we previously knew:
It would therefore not be surprising if further surveillance reveals a broad diversity of bat SL-CoVs that are able to use ACE2, some of which may have even closer homology to SARS-CoV than SL-CoV-WIV1.
Is there any implication of this work for the recently emerged MERS-CoV? Sequences related to MERS-CoV have been found in bats, and given that bats are known to be hosts of a number of viruses that infect humans, it is reasonable to postulate that MERS-CoV originated in bats. So far a 190 fragment of MERS-CoV nucleic acid has been found in a single bat from Saudi Arabia. Identification of the reservoir of MERS-CoV will require duplicating the methods reported in this paper: finding the complete viral genome, and infectious virus, in bats.
On episode #247 of the science show This Week in Virology, Ian Lipkin joins Vincent, Alan, Rich, and Kathy to describe how his laboratory is searching for the origin of MERS-coronavirus.
You can find TWiV #247 at www.microbe.tv/twiv.
What is wrong with this paragraph from today’s New York Times that describes the origin of the Middle East Respiratory Syndrome (MERS) coronavirus:
Health officials confirmed Wednesday that bats in Saudi Arabia were the source of the mysterious virus that has sickened 96 people in the Middle East, killing 47 of them.
Here is the science behind that statement, which has been published in Emerging Infectious Diseases. Samples (fecal, fecal swab, throat swab, blood) were collected from bats in an area of Saudi Arabia where human infections with MERS-CoV have been identified. Total nucleic acids were extracted and analyzed for the presence of coronavirus sequences by polymerase chain reaction. Coronavirus sequences were amplified from 220 of 732 fecal samples and 7 of 91 rectal swab samples or fecal pellets. One PCR product obtained from a single bat sample (fecal pellet of a T. perforatus bat captured in October 2012 in Bisha) had 100% nucleotide identity to a human MERS-CoV isolate.
A single PCR product 190 nucleotides in length from one bat was a perfect match with the genome sequence of a MERS-CoV isolate.
No infectious MERS-CoV has yet been isolated from this single bat. Therefore it is not yet possible to say that bats are the source of virus causing the MERS-CoV outbreak. As I have written previously, a virus is very different from a viral sequence.
It is certainly possible that MERS-CoV originated in a bat. Bats are known to harbor many viruses, and of course the SARS coronavirus originated in bats. But there is more than one explanation for the presence of this short viral sequence in bats. Perhaps the virus (or viral sequence) was obtained when the bat ingested a meal. Perhaps the 190 nucleotides are from a recombinant virus that is not MERS-CoV. I can think of other reasons why bats might not be the source of MERS-CoV.
For these reasons I believe that it is inaccurate for ‘health officials’ and the New York Times to confirm that bats are the source of MERS-CoV. Additional work is clearly needed to show that T. perforatus is the source of MERS-CoV, including isolation of infectious virus from bats and demonstrating infection of bats by the presence of antibodies to the virus. The work is in clearly progress; indeed the results might even be known, but they are not included in the Emerging Infectious Diseases article on which the NY Times piece was based.
Update 1: The term ‘frag-virus’ was proposed in 2008 to indicate viruses known only from sequence data. Although the term never caught on, the short article points out the problems that arise when genomic fragments are used to identify new viruses :
Although unintentional, these reports may mislead the readership of scientific journals and the general press. Having no distinction between preliminary genome-based evidence and conclusive proof by biological isolation and characterization of a replication-competent virus blurs the meaning of new virus.
Update 2: A phylogenetic analysis of the DNA fragment amplified from T. perforatus has been carried out. The author writes that “although this fragment means a very close relative of the human MERS-CoV is found in a bat geographically close to the first case, the fact it is identical in this short region doesn’t mean that these bats are the direct source of the human case.”  I would add even more uncertainty because we have no evidence that the virus was replicating in this single bat.
On episode #239 of the science show This Week in Virology, Matt joins Vincent, Alan, and Rich to summarize what we know and what we do not know about the MERS coronavirus.
You can find TWiV #239 at www.microbe.tv/twiv.