Identification of spike protein residues of murine coronavirus responsible for receptor-binding activity by use of soluble receptor-resistant mutants

Saeki, Keiichi; Ohtsuka, Nobuhisa; Taguchi, Fumihiro

doi:10.1128/jvi.71.12.9024-9031.1997

Cited by 70 publications

(108 citation statements)

References 49 publications

(82 reference statements)

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“…The observation that the different domains of the S protein all contribute to the tropism of CoVs is indicative of a coordinated interplay between these domains. This interplay has also been inferred from several studies, which reported changes in one S protein subunit often to be accompanied by adaptations in the other subunit (Saeki et al, 1997;Wang et al, 1992). In addition, the interplay between S 1 and S 2 has also been shown to be important for changes in the tropism of the virus as indicated earlier (de Haan et al, 2006;Navas-Martin et al, 2005).…”

Section: Discussionsupporting

confidence: 53%

“…A L1114F substitution in the MHV-JHM S protein was observed in a mutant strain of JHM and correlated with an increased S 1 -S 2 stability and the loss of the ability to induce CEACAM1aindependent fusion (Taguchi and Matsuyama, 2002), while a substitution of the same residue to an Arg (L1114R) reduced the neurotropism of this virus (Tsai et al, 2003). Mutants resistant to a monoclonal antibody (Wang et al, 1992) and soluble receptor (Saeki et al, 1997) also correlate with substitutions at this specific residue, illustrating the importance of this residue in S fusogenicity. For the MERS-CoV, mutations in HR1 have been identified that are thought to be associated with its adaptive evolution (Forni et al, 2015).…”

Section: Other S 2 Mutations Associated With Altered Tropismmentioning

confidence: 98%

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Coronavirus Spike Protein and Tropism Changes

2016

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Coronaviruses (CoVs) have a remarkable potential to change tropism. This is particularly illustrated over the last 15 years by the emergence of two zoonotic CoVs, the severe acute respiratory syndrome (SARS)- and Middle East respiratory syndrome (MERS)-CoV. Due to their inherent genetic variability, it is inevitable that new cross-species transmission events of these enveloped, positive-stranded RNA viruses will occur. Research into these medical and veterinary important pathogens-sparked by the SARS and MERS outbreaks-revealed important principles of inter- and intraspecies tropism changes. The primary determinant of CoV tropism is the viral spike (S) entry protein. Trimers of the S glycoproteins on the virion surface accommodate binding to a cell surface receptor and fusion of the viral and cellular membrane. Recently, high-resolution structures of two CoV S proteins have been elucidated by single-particle cryo-electron microscopy. Using this new structural insight, we review the changes in the S protein that relate to changes in virus tropism. Different concepts underlie these tropism changes at the cellular, tissue, and host species level, including the promiscuity or adaptability of S proteins to orthologous receptors, alterations in the proteolytic cleavage activation as well as changes in the S protein metastability. A thorough understanding of the key role of the S protein in CoV entry is critical to further our understanding of virus cross-species transmission and pathogenesis and for development of intervention strategies.

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Section: Discussionsupporting

confidence: 53%

Section: Other S 2 Mutations Associated With Altered Tropismmentioning

confidence: 98%

Coronavirus Spike Protein and Tropism Changes

2016

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“…In coronavirus infections, when processes of virus attachment and entry cannot be distinguished from each other, a concerted action between S1 and S2 has been observed. For example, the extended host range of MHV strains often requires a combination of mutations in S1 and S2 (de Haan et al, 2006;Navas-Martin et al, 2005;Saeki et al, 1997;Schickli et al, 2004;Thackray and Holmes, 2004). When elucidated in more detail, the communication between these regions was particularly contributing to virus-cell fusion and spread of progeny virus.…”

Section: Discussionmentioning

confidence: 99%

Contributions of the S2 spike ectodomain to attachment and host range of infectious bronchitis virus

et al. 2013

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The spike protein is the major viral attachment protein of the avian coronavirus infectious bronchitis virus (IBV) and ultimately determines viral tropism. The S1 subunit of the spike is assumed to be required for virus attachment. However, we have previously shown that this domain of the embryo- and cell culture adapted Beaudette strain, in contrast to that of the virulent M41 strain, is not sufficient for binding to chicken trachea (Wickramasinghe et al., 2011). In the present study, we demonstrated that the lack of binding of Beaudette S1 was not due to absence of virus receptors on this tissue nor due to the production of S1 from mammalian cells, as S1 proteins expressed from chicken cells also lacked the ability to bind IBV-susceptible embryonic tissue. Subsequently, we addressed the contribution of the S2 subunit of the spike in IBV attachment. Recombinant IBV Beaudette spike ectodomains, comprising the entire S1 domain and the S2 ectodomain, were expressed and analyzed for binding to susceptible embryonic chorio-allantoic membrane (CAM) in our previously developed spike histochemistry assay. We observed that extension of the S1 domain with the S2 subunit of the Beaudette spike was sufficient to gain binding to CAM. A previously suggested heparin sulfate binding site in Beaudette S2 was not required for the observed binding to CAM, while sialic acids on the host tissues were essential for the attachment. To further elucidate the role of S2 the spike ectodomains of virulent IBV M41 and chimeras of M41 and Beaudette were analyzed for their binding to CAM, chicken trachea and mammalian cell lines. While the M41 spike ectodomain showed increased attachment to both CAM and chicken trachea, no binding to mammalian cells was observed. In contrast, Beaudette spike ectodomain had relatively weak ability to bind to chicken trachea, but displayed marked extended host range to mammalian cells. Binding patterns of chimeric spike ectodomains to these tissues and cells indicate that S2 subunits most likely do not contain an additional independent receptor-binding site. Rather, the interplay between S1 and S2 subunits of spikes from the same viral origin might finally determine the avidity and specificity of virus attachment and thus viral host range.

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“…For several coronaviruses the receptor-binding site in S1 has been mapped. For MHV strain JHM (MHV-JHM), for instance, it was located in the domain composed of the amino-terminal 330 residues of the S molecule (Kubo et al, 1994), residues 62-65 and 214-216 being particularly important (Saeki et al, 1997;Suzuki and Taguchi, 1996). This amino-terminal domain also determined CEACAM1 receptor specificity of various MHV strains (Tsai et al, 2003).…”

Section: F S Proteinmentioning

confidence: 99%