MEDICINE FOR ALL

Bats are likely natural reservoirs of MERS-CoV or an ancestral MERS-like CoV. It is hypothesized that bat MERS-like CoV jumped to camels or some other as yet unidentified animal several decades ago. The virus evolved and adapted with accumulating  mutations in camels and then was transmitted to humans very recently.  It took almost a decade from the first discovery of SL-CoV in bats to the final isolation of the SARS-CoV ancestral virus  from bats, so continuing surveillance is vital to uncover the origin of MERS-CoV and  bats should certainly be a priority of research.

Bats harbor coronaviruses  with great genetic diversity. It is believed that most, if not all, currently circulating alphacoronaviruses and betacoronaviruses in different mammals are evolutionally linked to ancestral coronaviruses  originated from bats. Different species of rhinolophid bats  in China carry genetically diverse SARS-like coronaviruses, some of which are direct ancestors of SARS-CoV and hence have the potential to cause direct interspecies transmission to humans. Meanwhile, different coronavirus species closely related to MERS-CoV are circulating in bats.

Although the study of bat-borne coronaviruses has only started just about 15 years ago, the scientific community has already learnt a great deal of useful lessons which will be instrumental in mitigating , predicting, and preventing future zoonotic coronavirus outbreaks.

HCoV-NL63  was first isolated from babies suffering of pneumonia and bronchiolitis in 2004. HCoV-NL63 has been found worldwide with up to 9.3% detection rate in hospitalized respiratory tract samples. In 2010, a bat coronavirus termed ARCoV.2(Appalachian Ridge CoV) detected in  North American tricolored bat (Perimyotis subflavus) in the US showed close relationship  with HCoV-NL63. The MRCA for HCoV-NL63 and ARCoV.2 was predicted to have existed 563 to 822 years ago. Further analysis indicated that HCoV-NL63 can replicate in cell lines derived from the lungs of tricolored bats. These results suggest that prototypes of HCoV-NL63 may also exist in bats and there may also be a bat origin of this human coronavirus.

A recent study characterized more 229-E related coronaviruses  discovered in hipposiderid bats from Ghana on full genome level. These bat coronaviruses were more diverdiversified  and formed a single viral species with HCoV-229E. Interestingly, phylogenetic analysis revealed the intermediate position of a 229E-related alpaca virus between bat and human viruses. These findings suggested the ancestral origin of HCoV-229E in hipposiderid bats and the role of camelids as potential  intermediate hosts was hypothesized.

Bat coronaviruses and human coronavirus 229E(HCoV-229E) and NL63(HCoV-NL63)

HCoV-229 was found in the 1960s and causes comparatively mild common colds worldwide. A bat coronavirus detected in Hipposideros caffer ruber in genetically related to HCoV-229E. Its RdRp fragment shared 92% nucleotide sequence identity with HCoV-229E  and they were predicted to share a most recent common ancestor (MRCA) only 200 years ago.

It is difficult to adopt the same strategy of SARS-CoV control in the prevention of future MERS-CoV outbreaks. Until a comprehensive approach is found, which most likely will involve the effective vaccination of camels against MERS-CoV among other measures, it is envisaged that sporadic human infection  will persist for some time in the future.