Difference in Receptor Usage between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-Like Coronavirus of Bat Origin
Wuze Ren, Xiuxia Qu, Wendong Li, Zhenggang Han, Meng Yu, Peng Zhou, Shu-Yi Zhang, Lin-Fa Wang, Hongkui Deng, Zhengli Shi
In this study we investigated the receptor usage of the (SL=Sars-related) SL-CoV S by combining a human immunodeficiency virus-based pseudovirus system with cell lines expressing the ACE2 molecules of human, civet or horseshoe bat. In addition to full-length S of SL-CoV and SARS-CoV, a series of S chimeras was constructed by inserting different sequences of the SARS-CoV S into the SL-CoV S backbone. Several important observations were made from this study. First, the SL-CoV S was unable to use any of the three ACE2 molecules as its receptor. Second, the SARS-CoV S failed to enter cells expressing the bat ACE2. Third, the chimeric S covering the previously defined receptor-binding domain gained its ability to enter cells via human ACE2, albeit with different efficiencies for different constructs. Fourth, a minimal insert region (amino acids 310 to 518) was found to be sufficient to convert the SL-CoV S from non-ACE2 binding to human ACE2 binding, indicating that the SL-CoV S is largely compatible with SARS-CoV S protein both in structure and in function. The significance of these findings in relation to virus origin, virus recombination, and host switching is discussed….
However, when the RBD of SL-CoV S was replaced with that from the SARS-CoV S, the hybrid S protein was able to use the huACE2 for cell entry, implying that the SL-CoV S proteins are structurally and functionally very similar to the SARS-CoV S. These results suggest that although the SL-CoVs discovered in bats so far are unlikely to infect humans using ACE2 as a receptor, it remains to be seen whether they are able to use other surface molecules of certain human cell types to gain entry. It is also conceivable that these viruses may become infectious to humans if they undergo N-terminal sequence variation, for example, through recombination with other CoVs, which in turn might lead to a productive interaction with ACE2 or other surface proteins on human cells. https://jvi.asm.org/content/82/4/1899
………………………………………..….
J Virol. 2008 Feb; 82(4): 1899–1907.
Published online 2007 Dec 12.
Difference in Receptor Usage between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-Like Coronavirus of Bat Origin▿
Wuze Ren,1,† Xiuxia Qu,2,† Wendong Li,1,‡ Zhenggang Han,1 Meng Yu,3 Peng Zhou,1 Shu-Yi Zhang,4 Lin-Fa Wang,3,* Hongkui Deng,2 and Zhengli Shi1,*
Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor of SARS-CoV, and the molecular interaction between ACE2 and the SARS-CoV S protein has been well characterized (27, 28, 31, 42). A 193-residue fragment (amino acids [aa] 318 to 510) in the SARS-CoV S protein was demonstrated to be the minimal receptor-binding domain (RBD) which alone was able to efficiently bind to ACE2 (1, 42a, 45). Furthermore, it was shown that minor changes in amino acid residues of the receptor-binding motif (RBM) of SARS-CoV S protein could abolish the entry of SARS-CoV into cells expressing human ACE2 (huACE2) (7, 31). In the corresponding RBD region of the SL-CoV S proteins, there is significant sequence divergence from those of the SARS-CoV S proteins, including two deletions of 5 and 12 or 13 aa. From crystal-structural analysis of the S-ACE2 complex, it was predicted that the S protein of SL-CoV is unlikely to use huACE2 as an entry receptor (30), although this has never been experimentally proven due to the lack of live SL-CoV isolates. Whether it is possible to construct an ACE2-binding SL-CoV S protein by replacing the RBD with that from SARS-CoV S proteins is also unknown.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2258702/
No comments:
Post a Comment