Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus

Abstract

The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family Vespertilionidae. Here, we describe a MERS-like CoV identified from a Pipistrellus cf. hesperidus bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Indeed, several amino acid substitutions were identified in key binding residues that were predicted to block PREDICT/PDF-2180 from attaching to the MERS-CoV DPP4 receptor. To experimentally test this hypothesis, an infectious MERS-CoV clone expressing the PREDICT/PDF-2180 spike protein was generated. Recombinant viruses derived from the clone were replication competent but unable to spread and establish new infections in Vero cells or primary human airway epithelial cells. Our findings suggest that PREDICT/PDF-2180 is unlikely to pose a zoonotic threat. Recombination in the S1 subunit of the spike gene was identified as the primary mechanism driving variation in the spike phenotype and was likely one of the critical steps in the evolution and emergence of MERS-CoV in humans.

Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection

“…Bats are reservoirs of several emerging RNA viruses, such as filoviruses (ebolavirus and Marburg virus), paramyxoviruses (Nipah and Hendra viruses), and coronaviruses (severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS] coronaviruses [CoVs]) that cause serious and often fatal disease in humans and agricultural animals (Anthony et al, 2017;Forbes et al, 2019;Ge et al, 2013;Swanepoel et al, 2007;Yang et al, 2019). More recently, SARS-CoV-2, which is causing the ongoing COVID-19 outbreak, was determined to be 96% similar at the genomic level to a bat CoV (Bat_CoV_RaTG13) that was detected in Rhinolophus affinis (Zhou et al, 2020).…”

Advances in respiratory virus therapeutics – A meeting report from the 6th isirv Antiviral Group conference

“…The highly pathogenic human coronaviruses SARS-CoV and MERS-CoV originated in bat zoonotic reservoirs and then passed through different intermediate hosts prior to infecting humans. Bat coronavirus strains that share varying homology to MERS-and SARS-CoV are still circulating and represent the pre-epidemic strains most likely to make the jump into humans (Anthony et al, 2017;Becker et al, 2008;Menachery et al, 2015Menachery et al, , 2016Sheahan et al, 2008aSheahan et al, , 2008b. As many novel bat coronavirus strains were identified solely as genomic sequence isolated from bat guano, characterization of these strains beyond sequence analysis was not initially possible.…”

Encephalomyocarditis virus is potentially derived from eastern bent-wing bats living in East Asian countries

“…Bats are considered natural reservoirs for several zoonotic viruses including lyssaviruses (Davis et al, 2013a, b;Albas et al, 2011;Almeida et al, 2011Almeida et al, , 2005, henipaviruses (Roche et al, 2015;Breed et al, 2011;Rahman et al, 2010), coronaviruses (Anthony et al, 2017; T coronavirus (MERS-CoV) that was first reported in Saudi Arabia , and severe acute respiratory syndrome coronavirus (SARS-CoV) that caused outbreaks in China in 2003 (Ge et al, 2016(Ge et al, , 2013Balboni et al, 2012;Wang et al, 2006). A novel coronavirus, which is closely related to SARS-CoV and uses Angiotensin Converting Enzyme 2 (ACE-2) receptor from humans, civets, and Chinese horseshoe bats for cell entry, was isolated from Chinese horseshoe bats suggesting these bats might be natural reservoirs of SARS-CoV (Ge et al, 2013).…”