SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape.
SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape.
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DOI：
10.1016/j.cell.2021.02.042
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发表时间：
2021-04-29
期刊：
影响因子：
64.5
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Li Q;Nie J;Wu J;Zhang L;Ding R;Wang H;Zhang Y;Li T;Liu S;Zhang M;Zhao C;Liu H;Nie L;Qin H;Wang M;Lu Q;Li X;Liu J;Liang H;Shi Y;Shen Y;Xie L;Zhang L;Qu X;Xu W;Huang W;Wang Y
SARS-CoV-2的501Y.V2变种含有SPEKE的多个突变，目前在南非占主导地位，并正在迅速传播到其他国家。在这里，用18种假型病毒进行的实验表明，501Y.V2变异体在多种细胞类型中不会增加传染性，但小鼠ACE2过度表达的细胞除外，在那里观察到传染性显著增加。值得注意的是，501Y.V2变异体对17个中和性单抗中的12个的敏感度显著降低，这些变异体对恢复期患者和免疫小鼠的血清的中和能力也降低。中和抗性主要由SPEKE受体结合区的E484K和N501Y突变引起。小鼠ACE2过度表达细胞的感染性增强表明501Y.V2变体有可能溢出到小鼠。此外，我们检测到的501Y.V2变异株的中和抵抗力表明，单抗和疫苗的效力可能会受到影响。与614G变种501Y相比，501Y.V2在携带hACE2的细胞中的感染性并不高。与614G变种501Y相比，501Y.V2在携带mACE2的细胞中的感染性增加。V2逃避了大多数中和单抗501Y的中和作用。V2显著削弱了多克隆抗体的抑制作用。用伪型病毒进行的实验表明，SARS-CoV-2的501Y.V2变种对单抗和恢复期及免疫者血清的中和表现出抵抗力，主要是由于病毒刺突蛋白受体结合域的E484K和N501Y突变。
The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed. Notably, the susceptibility of the 501Y.V2 variants to 12 of 17 neutralizing monoclonal antibodies was substantially diminished, and the neutralization ability of the sera from convalescent patients and immunized mice was also reduced for these variants. The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of spike. The enhanced infectivity in murine ACE2-overexpressing cells suggests the possibility of spillover of the 501Y.V2 variants to mice. Moreover, the neutralization resistance we detected for the 501Y.V2 variants suggests the potential for compromised efficacy of monoclonal antibodies and vaccines. 501Y.V2 showed no higher infectivity in cells with hACE2 comparing to 614G variant 501Y.V2 showed increased infectivity in cells with mACE2 compared to 614G variant 501Y.V2 escaped neutralization by most of neutralizing monoclonal antibodies 501Y.V2 significantly compromised the inhibitory effects of polyclonal antibodies Experiments with pseudotyped viruses show that the 501Y.V2 variant of SARS-CoV-2 exhibits resistance to neutralization from monoclonal antibodies and sera from convalescent as well as immunized individuals, predominantly due to the E484K and N501Y mutations in the receptor-binding domain of the viral spike protein.
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影响因子：
64.8
作者：
Plante JA;Liu Y;Liu J;Xia H;Johnson BA;Lokugamage KG;Zhang X;Muruato AE;Zou J;Fontes-Garfias CR;Mirchandani D;Scharton D;Bilello JP;Ku Z;An Z;Kalveram B;Freiberg AN;Menachery VD;Xie X;Plante KS;Weaver SC;Shi PY
通讯作者：
Shi PY
DOI：
10.1016/s2213-2600(21)00005-9
发表时间：
2021-03
期刊：
The Lancet. Respiratory medicine
影响因子：
--
作者：
Kirby T
通讯作者：
Kirby T
DOI：
10.1126/science.abe8499
发表时间：
2020-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hou YJ;Chiba S;Halfmann P;Ehre C;Kuroda M;Dinnon KH 3rd;Leist SR;Schäfer A;Nakajima N;Takahashi K;Lee RE;Mascenik TM;Graham R;Edwards CE;Tse LV;Okuda K;Markmann AJ;Bartelt L;de Silva A;Margolis DM;Boucher RC;Randell SH;Suzuki T;Gralinski LE;Kawaoka Y;Baric RS
通讯作者：
Baric RS
DOI：
10.1126/science.abc4730
发表时间：
2020-09-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gu H;Chen Q;Yang G;He L;Fan H;Deng YQ;Wang Y;Teng Y;Zhao Z;Cui Y;Li Y;Li XF;Li J;Zhang NN;Yang X;Chen S;Guo Y;Zhao G;Wang X;Luo DY;Wang H;Yang X;Li Y;Han G;He Y;Zhou X;Geng S;Sheng X;Jiang S;Sun S;Qin CF;Zhou Y
通讯作者：
Zhou Y
影响因子：
56.9
作者：
Lv, Zhe;Deng, Yong-Qiang;Wang, Xiangxi
通讯作者：
Wang, Xiangxi