Link of a ubiquitous human coronavirus to dromedary camels

Abstract

The four human coronaviruses (HCoVs) are globally endemic respiratory pathogens. The Middle East respiratory syndrome (MERS) coronavirus (CoV) is an emerging CoV with a known zoonotic source in dromedary camels. Little is known about the origins of endemic HCoVs. Studying these viruses’ evolutionary history could provide important insight into CoV emergence. In tests of MERS-CoV–infected dromedaries, we found viruses related to an HCoV, known as HCoV-229E, in 5.6% of 1,033 animals. Human- and dromedary-derived viruses are each monophyletic, suggesting ecological isolation. One gene of dromedary viruses exists in two versions in camels, full length and deleted, whereas only the deleted version exists in humans. The deletion increased in size over a succession starting from camelid viruses via old human viruses to contemporary human viruses. Live isolates of dromedary 229E viruses were obtained and studied to assess human infection risks. The viruses used the human entry receptor aminopeptidase N and replicated in human hepatoma cells, suggesting a principal ability to cause human infections. However, inefficient replication in several mucosa-derived cell lines and airway epithelial cultures suggested lack of adaptation to the human host. Dromedary viruses were as sensitive to the human type I interferon response as HCoV-229E. Antibodies in human sera neutralized dromedary-derived viruses, suggesting population immunity against dromedary viruses. Although no current epidemic risk seems to emanate from these viruses, evolutionary inference suggests that the endemic human virus HCoV-229E may constitute a descendant of camelid-associated viruses. HCoV-229E evolution provides a scenario for MERS-CoV emergence.

Origin and evolution of pathogenic coronaviruses

“…HCoV-229E and HCoV-NL63 usually cause mild infections in immunocompetent humans. Progenitors of these viruses have recently been found in African bats133,134 , and the camelids are likely intermediate hosts of HCoV-229E134,135 .…”

Interplay between co-divergence and cross-species transmission in the evolutionary history of bat coronaviruses

“…The MERS epidemic is ongoing in the Middle East and travel-associated cases have been reported in 27 countries worldwide (WHO, 2017). Finally, Alphacoronavirus 229E and NL63, which cause a mild influenza-like syndrome in humans, share a common ancestor with viruses sampled from the bat genus Hipposideros and Triaenops, respectively (Corman et al, 2015(Corman et al, , 2016Tao et al, 2017).…”

Human coronaviruses and other respiratory infections in young adults on a university campus: Prevalence, symptoms, and shedding

“…By contrast, 4 other human coronaviruses (HCoVs), 229E, HKU1, NL63, and OC43, already circulate globally, but generally have low fatality rates . These 4 HCoVs also are believed to be derived from zoonotic sources, including bats (NL63, 229E), dromedary camels (299E), or cattle (OC43), although the origins of HKU1 remain uncertain …”