tetano
Editor, Senior Moderator
mBio
. 2023 Apr 3;e0041623.
doi: 10.1128/mbio.00416-23. Online ahead of print.
Evolution of Immune Evasion and Host Range Expansion by the SARS-CoV-2 B.1.1.529 (Omicron) Variant
Wenlin Ren[SUP] #[/SUP][SUP] 1 [/SUP], Yu Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Juhong Rao[SUP] #[/SUP][SUP] 2 3 [/SUP], Ziyi Wang[SUP] 4 [/SUP], Jun Lan[SUP] 4 [/SUP], Kunpeng Liu[SUP] 2 3 [/SUP], Xuekai Zhang[SUP] 2 3 [/SUP], Xue Hu[SUP] 2 [/SUP], Chen Yang[SUP] 1 [/SUP], Guocai Zhong[SUP] 5 6 [/SUP], Rong Zhang[SUP] 7 [/SUP], Xinquan Wang[SUP] 4 [/SUP], Chao Shan[SUP] 2 [/SUP], Qiang Ding[SUP] 1 [/SUP]
Affiliations
Abstract
Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 (Omicron) has rapidly become the dominant strain, with an unprecedented number of mutations within its spike gene. However, it remains unknown whether these variants have alterations in their entry efficiency, host tropism, and sensitivity to neutralizing antibodies and entry inhibitors. In this study, we found that Omicron spike has evolved to escape neutralization by three-dose inactivated-vaccine-elicited immunity but remains sensitive to an angiotensin-converting enzyme 2 (ACE2) decoy receptor. Moreover, Omicron spike could use human ACE2 with a slightly increased efficiency while gaining a significantly increased binding affinity for a mouse ACE2 ortholog, which exhibits limited binding with wild-type (WT) spike. Furthermore, Omicron could infect wild-type C57BL/6 mice and cause histopathological changes in the lungs. Collectively, our results reveal that evasion of neutralization by vaccine-elicited antibodies and enhanced human and mouse ACE2 receptor engagement may contribute to the expanded host range and rapid spread of the Omicron variant. IMPORTANCE The recently emerged SARS-CoV-2 Omicron variant with numerous mutations in the spike protein has rapidly become the dominant strain, thereby raising concerns about the effectiveness of vaccines. Here, we found that the Omicron variant exhibits a reduced sensitivity to serum neutralizing activity induced by a three-dose inactivated vaccine but remains sensitive to entry inhibitors or an ACE2-Ig decoy receptor. Compared with the ancestor strain isolated in early 2020, the spike protein of Omicron utilizes the human ACE2 receptor with enhanced efficiency while gaining the ability to utilize mouse ACE2 for cell entry. Moreover, Omicron could infect wild-type mice and cause pathological changes in the lungs. These results reveal that antibody evasion, enhanced human ACE2 utilization, and an expanded host range may contribute to its rapid spread.
Keywords: ACE2 decoy receptor; B.1.1.529; COVID-19; Omicron variant; SARS-CoV-2; host range.
. 2023 Apr 3;e0041623.
doi: 10.1128/mbio.00416-23. Online ahead of print.
Evolution of Immune Evasion and Host Range Expansion by the SARS-CoV-2 B.1.1.529 (Omicron) Variant
Wenlin Ren[SUP] #[/SUP][SUP] 1 [/SUP], Yu Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Juhong Rao[SUP] #[/SUP][SUP] 2 3 [/SUP], Ziyi Wang[SUP] 4 [/SUP], Jun Lan[SUP] 4 [/SUP], Kunpeng Liu[SUP] 2 3 [/SUP], Xuekai Zhang[SUP] 2 3 [/SUP], Xue Hu[SUP] 2 [/SUP], Chen Yang[SUP] 1 [/SUP], Guocai Zhong[SUP] 5 6 [/SUP], Rong Zhang[SUP] 7 [/SUP], Xinquan Wang[SUP] 4 [/SUP], Chao Shan[SUP] 2 [/SUP], Qiang Ding[SUP] 1 [/SUP]
Affiliations
- PMID: 37010428
- DOI: 10.1128/mbio.00416-23
Abstract
Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 (Omicron) has rapidly become the dominant strain, with an unprecedented number of mutations within its spike gene. However, it remains unknown whether these variants have alterations in their entry efficiency, host tropism, and sensitivity to neutralizing antibodies and entry inhibitors. In this study, we found that Omicron spike has evolved to escape neutralization by three-dose inactivated-vaccine-elicited immunity but remains sensitive to an angiotensin-converting enzyme 2 (ACE2) decoy receptor. Moreover, Omicron spike could use human ACE2 with a slightly increased efficiency while gaining a significantly increased binding affinity for a mouse ACE2 ortholog, which exhibits limited binding with wild-type (WT) spike. Furthermore, Omicron could infect wild-type C57BL/6 mice and cause histopathological changes in the lungs. Collectively, our results reveal that evasion of neutralization by vaccine-elicited antibodies and enhanced human and mouse ACE2 receptor engagement may contribute to the expanded host range and rapid spread of the Omicron variant. IMPORTANCE The recently emerged SARS-CoV-2 Omicron variant with numerous mutations in the spike protein has rapidly become the dominant strain, thereby raising concerns about the effectiveness of vaccines. Here, we found that the Omicron variant exhibits a reduced sensitivity to serum neutralizing activity induced by a three-dose inactivated vaccine but remains sensitive to entry inhibitors or an ACE2-Ig decoy receptor. Compared with the ancestor strain isolated in early 2020, the spike protein of Omicron utilizes the human ACE2 receptor with enhanced efficiency while gaining the ability to utilize mouse ACE2 for cell entry. Moreover, Omicron could infect wild-type mice and cause pathological changes in the lungs. These results reveal that antibody evasion, enhanced human ACE2 utilization, and an expanded host range may contribute to its rapid spread.
Keywords: ACE2 decoy receptor; B.1.1.529; COVID-19; Omicron variant; SARS-CoV-2; host range.