Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species

Zhang, Hong Liang; Li, Yu Ming; Sun, Jing; Zhang, Yu Yuan; Wang, Tong Yun; Sun, Ming; Wang, Meng Hang; Yang, Yue; Hu, Xiao Liang; Tang, Yan; Zhao, Jincun; Cai, Xuehui

doi:10.1016/j.jbc.2021.100435

Cited by 37 publications

(44 citation statements)

References 33 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The primary entry receptor for SARS-CoV-2 is the Angiotensin-converting enzyme 2 (ACE2). A recent study indicated that the ACE2 of dogs facilitated SARS-CoV-2 entry into nonsusceptible cells ( 64 ). Significantly, SARS-CoV-2 was detected from two dogs which lived with the diagnosed humans, while the dogs remained asymptomatic during quarantine ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

The Gut Viral Metagenome Analysis of Domestic Dogs Captures Snapshot of Viral Diversity and Potential Risk of Coronavirus

Shi

Tao

et al. 2021

Front. Vet. Sci.

View full text Add to dashboard Cite

The close relations between dogs (Canis lupus familiaris) and humans lay a foundation for cross species transmissions of viruses. The co-existence of multiplex viruses in the host accelerate viral variations. For effective prediction and prevention of potential epidemic or even pandemic, the metagenomics method was used to investigate the gut virome status of 45 domestic healthy dogs which have extensive contact with human beings. A total of 248.6 GB data (505, 203, 006 valid reads, 150 bp in length) were generated and 325, 339 contigs, which were best matched with viral genes, were assembled from 46, 832, 838 reads. In the aggregate, 9,834 contigs (3.02%) were confirmed for viruses. The top 30 contigs with the most reads abundance were mapped to DNA virus families Circoviridae, Parvoviridae and Herpesviridae; and RNA virus families Astroviridae, Coronaviridae and Picornaviridae, respectively. Numerous sequences were assigned to animal virus families of Astroviridae, Coronaviridae, Circoviridae, etc.; and phage families of Microviridae, Siphoviridae, Ackermannviridae, Podoviridae, Myoviridae and the unclassified phages. Further, several sequences were homologous with the insect and plant viruses, which reflects the diet and habitation of dogs. Significantly, canine coronavirus was uniquely identified in all the samples with high abundance, and the phylogenetic analysis therefore showed close relationship with the human coronavirus strain 229E and NL63, indicating the potential risk of canine coronavirus to infect humans by obtaining the ability of cross-species transmission. This study emphasizes the high detection frequency of virus harbored in the enteric tract of healthy contacted animal, and expands the knowledge of the viral diversity and the spectrum for further disease-association studies, which is meaningful for elucidating the epidemiological and biological role of companion animals in public health.

show abstract

Section: Discussionmentioning

confidence: 99%

The Gut Viral Metagenome Analysis of Domestic Dogs Captures Snapshot of Viral Diversity and Potential Risk of Coronavirus

Shi

Tao

et al. 2021

Front. Vet. Sci.

View full text Add to dashboard Cite

show abstract

“…Two swine cell lines, swine testicular and porcine kidney cells, were also found to develop CPE after several passages of virus. Multiple studies have also used different mammalian cell lines and transfected them with the swine ACE2 gene to allow for transient expression of the gene, and most found that SC2 or a SC2 pseudovirus could attach to and express protein in the cell as measured by several different methods (2, 4, 44, 53). This predictive data based on ACE2 data from some species, such as swine, suggest susceptibility to infection, although our results in DF1 cells did not show evidence of virus replication.…”

Section: Discussionmentioning

confidence: 99%

“…The surprising result is the potential susceptibility of goats. Goats have not been known to be naturally or experimentally infected at this time, but one study has previously suggested that SC2 can infect HEK cells that are expressing goat ACE2 (53).…”

Section: Discussionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted August 19, 2021. ; https://doi.org/10.1101/2021.08.18.456916 doi: bioRxiv preprint transfected them with the swine ACE2 gene to allow for transient expression of the gene, and most found that SC2 or a SC2 pseudovirus could attach to and express protein in the cell as measured by several different methods (2,4,44,53). This predictive data based on ACE2 data from some species, such as swine, suggest susceptibility to infection, although our results in DF1 cells did not show evidence of virus replication.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of an in vitro model for animal species susceptibility to SARS-CoV-2 replication based on expression of ACE2 and TMPRSS2 in avian cells

Kapczynski

Sweeney

Suarez

et al. 2021

Preprint

View full text Add to dashboard Cite

The SARS-CoV-2 (SC2) virus has caused a worldwide pandemic because of the virus’s ability to transmit efficiently human-to-human. A key determinant of infection is the attachment of the viral spike protein to the host receptor angiotensin-converting enzyme 2 (ACE2). Because of the presumed zoonotic origin of SC2, there is no practical way to assess every species susceptibility to SC2 by direct challenge studies. In an effort to have a better predictive model of animal host susceptibility to SC2, we expressed the ACE2 and/or transmembrane serine protease 2 (TMPRSS2) genes from humans and other animal species in the avian fibroblast cell line, DF1, that is not permissive to infection. We demonstrated that expression of both human ACE2 and TMPRSS2 genes is necessary to support SC2 infection and replication in DF1 and a non-permissive sub-lineage of MDCK cells. Titers of SC2 in these cell lines were comparable to those observed in control Vero cells. To further test the model, we developed seven additional transgenic cell lines expressing the ACE2 and TMPRSS2 derived from Felis (cat), Equus (horse), Sus (pig), Capra (goat), Mesocricetus (Golden hamster), Myotis lucifugus (Little Brown bat) and Hipposideros armiger (Great Roundleaf bat) in DF1 cells. Results demonstrate permissive replication of SC2 in cat, Golden hamster, and goat species, but not pig or horse, which correlated with the results of reported challenge studies. The development of this cell culture model allows for more efficient testing of the potential susceptibility of many different animal species for SC2 and emerging variant viruses.IMPORTANCESARS-CoV-2 (SC2) is believed to have originated in animal species and jumped into humans where it has produced the greatest viral pandemic of our time. Identification of animal species susceptible to SC2 infection would provide information on potential zoonotic reservoirs, and transmission potential at the human-animal interface. Our work provides a model system to test the ability of the virus to replicate in an otherwise non-permissive cell line by transgenic insertion of the ACE2 and TMPRSS2 genes from human and other animal species. The results from our in vitro model positively correlate with animal infection studies enhancing the predicative capability of the model. Importantly, we demonstrate that both proteins are required for successful virus replication. These findings establish a framework to test other animal species for susceptibility to infection that may be critical zoonotic reservoirs for transmission, as well as to test variant viruses that arise over time.

show abstract

“…Prior to a hypothetical spillover event, a recent ancestor to SARS-CoV-2 likely evolved inside bat host cells for many decades 3 . However, the natural evolution hypothesis of SARS-CoV-2 origin is currently not without considerable limitations: first, the difficulty in characterizing the evolutionary origin of the unusual polybasic (RRAR) furin cleavage site at the S1/S2 junction of the SARS-COV-2 spike (S) glycoprotein 4 ; second, the discrepancy between an exponentially suppressed tropism of SARS-CoV-2 in Rhinolophus sinicus bat cells 5 and the high susceptibility of SARS-CoV-2 toward cell entry via Rhinolophus sinicus angiotensin-converting enzyme 2, its primary entry receptor 6 ; and third, the persistent inability to identify an intermediate ancestral host between human and the horseshoe bat Rhinolophus affinis. This species was reported to be the host of coronavirus RaTG13 7,8 , currently the isolate with the highest sequence similarity to the SARS-CoV-2 genome, which is located on the same phylogenetic branch as Rhinolophus sinicus bat coronavirus 9 .…”

Section: Introductionmentioning

confidence: 99%

Differential enrichment of yeast DNA in SARS-CoV-2 and related genomes supports synthetic origin hypothesis

Lisewski

2021

F1000Res

View full text Add to dashboard Cite

Background: Knowledge about the origin of SARS-CoV-2 is necessary for both a biological and epidemiological understanding of the COVID-19 pandemic. Evidence suggests that a proximal evolutionary ancestor of SARS-CoV-2 belongs to the bat coronavirus family. However, as further evidence for a direct zoonosis remains limited, alternative modes of SARS-CoV-2 biogenesis should be also considered. Results: Here we show that genomes from SARS-CoV-2 and from closely related coronaviruses are differentially enriched with short chromosomal sequences from the yeast S. cerevisiae at focal positions that are known to be critical for virus replication, host cell invasion, and host immune response. Specifically, for SARS-CoV-2, we identify two sites: one at the start of the viral replicase domain, and the other at the end of the spike gene past its critical domain junction; for SARS-CoV-1, one at the start of the RNA dependent RNA polymerase gene, and the other at the start of the spike protein’s receptor binding domain. As yeast is not a natural host for this virus family, we propose a directed passage model for viral constructs, including virus replicase, in yeast cells based on co-transformation of virus DNA plasmids carrying yeast selectable genetic markers followed by intra-chromosomal homologous recombination through gene conversion. Highly differential sequence homology data across yeast chromosomes congruent with chromosomes harboring specific auxotrophic markers further support this passage model. Model and data together allow us to infer a hypothetical tripartite genome assembly scheme for the synthetic biogenesis of SARS-CoV-2 and SARS-CoV-1. Conclusions: These results provide evidence that the genome sequences of SARS-CoV-1, SARS-CoV-2, but not that of RaTG13 and all other closest SARS coronavirus family members identified, are carriers of distinct homology signals that might point to large-scale genomic editing during a passage of directed replication and chromosomal integration inside genetically modified yeast cells.

show abstract

Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species

Cited by 37 publications

References 33 publications

The Gut Viral Metagenome Analysis of Domestic Dogs Captures Snapshot of Viral Diversity and Potential Risk of Coronavirus

The Gut Viral Metagenome Analysis of Domestic Dogs Captures Snapshot of Viral Diversity and Potential Risk of Coronavirus

Development of an in vitro model for animal species susceptibility to SARS-CoV-2 replication based on expression of ACE2 and TMPRSS2 in avian cells

Differential enrichment of yeast DNA in SARS-CoV-2 and related genomes supports synthetic origin hypothesis

Contact Info

Product

Resources

About