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The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus by H.L Wells; M Letko; G Lasso; B Ssebide; J Nziza; D.K Byarugaba; I Navarrete-Macias; E Liang; M Cranfield; B.A Han; M.W Tingley; M Diuk-Wasser; T Goldstein; C.K Johnson; J Mazet; K Chandran; V.J Munster; K Gilardi; S.J Anthony is a scholarly article available to read on EtoBox.

What is The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus about?

SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda which are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination sc

Author

H.L Wells; M Letko; G Lasso; B Ssebide; J Nziza; D.K Byarugaba; I Navarrete-Macias; E Liang; M Cranfield; B.A Han; M.W Tingley; M Diuk-Wasser; T Goldstein; C.K Johnson; J Mazet; K Chandran; V.J Munster; K Gilardi; S.J Anthony

Publisher

Cold Spring Harbor Laboratory

Published

2021

Language

EN