Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic.
Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic.
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DOI：
10.1016/j.cell.2016.10.014
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发表时间：
2016-11-03
期刊：
影响因子：
64.5
通讯作者：
Luban, Jeremy
中科院分区：
文献类型：
--
作者：
Diehl, William E.;Lin, Aaron E.;Grubaugh, Nathan D.;Carvalho, Luiz Max;Kim, Kyusik;Kyawe, Pyae Phyo;McCauley, Sean M.;Donnard, Elisa;Kucukural, Alper;McDonel, Patrick;Schaffner, Stephen F.;Garber, Manuel;Rambaut, Andrew;Andersen, Kristian G.;Sabeti, Pardis C.;Luban, Jeremy
2013-2016年埃博拉病毒病（EVD）的流行程度使得在连续的人际传播事件中发生了前所未有的病毒突变，增加了在疫情期间发生适应人类宿主的可能性。我们研究了一种非同义突变，埃博拉病毒（EBOV）糖蛋白（GP）突变体A82 V，其对病毒感染性的影响。这种突变位于EBOV GP上的NPC 1结合位点，发生在2013-2016年爆发的早期，并上升到高频率。我们发现GP-A82 V感染灵长类细胞的能力增强，包括人类树突状细胞。增加的感染性仅限于在EBOV界面具有灵长类特异性NPC 1序列的细胞，这表明这种突变确实是对人类宿主的适应。GP-A82 V与死亡率增加相关，这与EVD流行期间GP-A82 V内在感染性增强导致疾病严重程度的假设一致。埃博拉病毒糖蛋白突变体GP-A82 V出现较早并主导西非流行病GP-A82 V比祖先糖蛋白更有效地感染人类细胞GP-A82 V的感染性增加对灵长类细胞具有特异性A82 V与流行期间死亡率增加的相关性较弱西非流行期间早期出现的埃博拉糖蛋白突变体增加了人类细胞的感染性，可能有助于死亡率上升
The magnitude of the 2013–2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP) mutant A82V, for its effect on viral infectivity. This mutation, located at the NPC1-binding site on EBOV GP, occurred early in the 2013–2016 outbreak and rose to high frequency. We found that GP-A82V had heightened ability to infect primate cells, including human dendritic cells. The increased infectivity was restricted to cells that have primate-specific NPC1 sequences at the EBOV interface, suggesting that this mutation was indeed an adaptation to the human host. GP-A82V was associated with increased mortality, consistent with the hypothesis that the heightened intrinsic infectivity of GP-A82V contributed to disease severity during the EVD epidemic. Ebola glycoprotein mutant GP-A82V arose early and dominated the West African epidemic GP-A82V infects human cells more efficiently than does the ancestral glycoprotein The increased infectivity of GP-A82V is specific for primate cells GP-A82V was weakly associated with increased mortality during the epidemic An Ebola glycoprotein mutant that arose early during the West African epidemic increases infectivity of human cells and may have contributed to increased mortality
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影响因子：
5.3
作者：
Arias A;Watson SJ;Asogun D;Tobin EA;Lu J;Phan MVT;Jah U;Wadoum REG;Meredith L;Thorne L;Caddy S;Tarawalie A;Langat P;Dudas G;Faria NR;Dellicour S;Kamara A;Kargbo B;Kamara BO;Gevao S;Cooper D;Newport M;Horby P;Dunning J;Sahr F;Brooks T;Simpson AJH;Groppelli E;Liu G;Mulakken N;Rhodes K;Akpablie J;Yoti Z;Lamunu M;Vitto E;Otim P;Owilli C;Boateng I;Okoror L;Omomoh E;Oyakhilome J;Omiunu R;Yemisis I;Adomeh D;Ehikhiametalor S;Akhilomen P;Aire C;Kurth A;Cook N;Baumann J;Gabriel M;Wölfel R;Di Caro A;Carroll MW;Günther S;Redd J;Naidoo D;Pybus OG;Rambaut A;Kellam P;Goodfellow I;Cotten M
通讯作者：
Cotten M
影响因子：
64.8
作者：
Cote, Marceline;Misasi, John;Ren, Tao;Bruchez, Anna;Lee, Kyungae;Filone, Claire Marie;Hensley, Lisa;Li, Qi;Ory, Daniel;Chandran, Kartik;Cunningham, James
通讯作者：
Cunningham, James
影响因子：
2
作者：
Gelman, Andrew
通讯作者：
Gelman, Andrew
DOI：
10.1073/pnas.0505659102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Berthoux, L;Sebastian, S;Luban, J
通讯作者：
Luban, J
影响因子：
5.4
作者：
Diehl, William E.;Stansell, Elizabeth;Hunter, Eric
通讯作者：
Hunter, Eric