SARS receptor - Cell 652 Haghighat, A., and Sonenberg, N....

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Cell 652 Haghighat, A., and Sonenberg, N. (1997). J. Biol. Chem. 272 , 21677– the Urbani isolate (Rota et al., 2003). The observations 21680. that ACE2 specifically binds to S1, supports formation Hershey, P.E.C., McWhirter, S.M., Gross, J.D., Wagner, G., Alber, of syncytia due to cell fusion mediated by the interaction T., and Sachs, A.B. (1999). J. Biol. Chem. 274 , 21297–21304. with S, and mediates infection of cells otherwise ineffi- Marcotrigiano, J., Gingras, A.-C., Sonenberg, N., and Burley, S.K. cient for virus replication that can be inhibited by an (1997). Cell 89 , 951–961. anti-ACE2 antibody provide convincing evidence for its Marcotrigiano, J., Gingras, A.-C., Sonenberg, N., and Burley, S.K. receptor function. (1999). Mol. Cell 3 , 707–716. In a remarkable series of experiments, Li et al. not Matsuo, H., Li, H., McGuire, A.M., Fletcher, C.M., Gingras, A.-C., only identified the virus receptor, but also demonstrated Sonenberg, N., and Wagner, G. (1997). Nature Struct. Biol. 4 , key characteristics of the membrane fusion process me- 717–724. diated by the ACE2 interaction with S. First, they showed Scheper, G.C., and Proud, C.G. (2002). Eur. J. Biochem. 269 , 5350– that expression of recombinant ACE2 and S resulted in 5359. cell fusion at neutral pH. This finding suggests that low Ptushkina, M., von der Haar, T., Vasilescu, S., Frank, R., Birkenha ¨ger, pH and other viral proteins are not required for fusion. R., and McCarthy, J.E.G. (1998). EMBO J. 17 , 4798–4808. The S glycoprotein from another SARS-CoV isolate von der Haar, T., Ball, P.D., and McCarthy, J.E.G. (2000). J. Biol. (Tor2) can also mediate fusion at neutral pH (Xiao et al., Chem. 275 , 30551–30555. 2003), suggesting that the absence of a low pH require- ment to trigger fusion is not strain-specific, although more isolates should be tested. It has also been demon- strated that expression of recombinant S from some coronaviruses can lead to syncytia formation at neutral The Secret Life of ACE2 pH (Lai and Cavanagh, 1997). However, it remains possi- ble that low pH is important for uptake of cell-free virus. as a Receptor for the SARS Virus Second, the S glycoprotein was not cleaved to any mea- surable degree, but effects of cleavage at the cell sur- face by proteases on fusion cannot be excluded. Recent biochemical and functional data showed that coronavi- The membrane-associated carboxypeptidase angio- rus S glycoprotein is a class I fusion protein (Bosch et tensin-converting enzyme 2 (ACE2) is an essential reg- al., 2003); the lack of cleavage sets apart the SARS-CoV
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SARS receptor - Cell 652 Haghighat, A., and Sonenberg, N....

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