Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission.
Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission.
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DOI：
10.1038/s41598-018-33487-8
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发表时间：
2018-10-11
影响因子：
4.6
通讯作者：
Drosten C
中科院分区：
文献类型：
--
作者：
Muth D;Corman VM;Roth H;Binger T;Dijkman R;Gottula LT;Gloza-Rausch F;Balboni A;Battilani M;Rihtarič D;Toplak I;Ameneiros RS;Pfeifer A;Thiel V;Drexler JF;Müller MA;Drosten C
严重急性呼吸综合征冠状病毒（SARS-CoV）在人类中出现的最明显的基因变化是其开放阅读框8（ORF 8）中29个核苷酸的缺失。尽管进行了大量的研究，但仍不清楚这种缺失是否真的反映了对人类的适应。在这里，我们将完全、部分缺失（-29 nt）和完全缺失的ORF 8基因改造成SARS冠状病毒感染性cDNA克隆株法兰克福-1。在灵长类动物细胞培养物以及通过慢病毒转导人血管紧张素转换酶2受体而允许SARS-CoV复制的菊头蝠细胞中比较了所得病毒的复制。来自棉鼠、山羊和绵羊的细胞提供了代表SARS冠状病毒既不是地方病也不是流行病的宿主系统的对照方案。不依赖于细胞系统，ORF 8的截短（29 nt缺失）使复制降低高达23倍。该效应与I型干扰素反应无关。SARS-CoV中29个核苷酸的缺失是一种沿着最初的人传人链沿着获得的有害突变。由此产生的适应性丧失可能是由于创始人效应，这在病毒出现的过程中很少有记录。这些结果对SARS威胁的回顾性评估具有重要意义。
A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (−29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor. Cells from cotton rat, goat, and sheep provided control scenarios that represent host systems in which SARS-CoV is neither endemic nor epidemic. Independent of the cell system, the truncation of ORF8 (29 nt deletion) decreased replication up to 23-fold. The effect was independent of the type I interferon response. The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain. The resulting loss of fitness may be due to a founder effect, which has rarely been documented in processes of viral emergence. These results have important implications for the retrospective assessment of the threat posed by SARS.
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DOI：
10.1073/pnas.96.9.5095
发表时间：
1999-04-27
影响因子：
11.1
作者：
Bergstrom, CT;McElhany, P;Real, LA
通讯作者：
Real, LA
影响因子：
3.7
作者：
Eckerle I;Ehlen L;Kallies R;Wollny R;Corman VM;Cottontail VM;Tschapka M;Oppong S;Drosten C;Müller MA
通讯作者：
Müller MA
影响因子：
64.8
作者：
Jones KE;Patel NG;Levy MA;Storeygard A;Balk D;Gittleman JL;Daszak P
通讯作者：
Daszak P
影响因子：
12.4
作者：
Hofmann, A;Kessler, B;Pfeifer, A
通讯作者：
Pfeifer, A
影响因子：
64.5
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
通讯作者：
Luban, Jeremy