Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease.

Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease.
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DOI:
10.1016/j.virol.2010.01.004
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发表时间:
2010-03-30
期刊:
影响因子:
3.7
通讯作者:
Perlman S
Perlman S
中科院分区:
医学3区
文献类型:
--
作者:
Netland J;DeDiego ML;Zhao J;Fett C;Álvarez E;Nieto-Torres JL;Enjuanes L;Perlman S

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2002-2003年,严重急性呼吸道综合征冠状病毒(SARS-CoV)造成大量发病率和死亡率。删除包膜(E)蛋白适度减少了病毒在组织培养中的生长,但消除了动物中的毒力。在这里,我们表明,用rSARS-CoV-ΔE或SARS-CoV-Δ[E,6- 9 b](除了E之外,还删除了辅助蛋白(6,7a,7 b,8a,8b,9 b))免疫几乎完全保护BALB/c小鼠免受由小鼠适应的SARS-CoV引起的致命呼吸道疾病的影响,并部分保护hACE 2 Tg小鼠免受致命疾病的影响。表达人SARS-CoV受体的hACE 2 Tg小鼠对感染极其敏感。我们还发现rSARS-CoV-ΔE和rSARS-CoV-Δ[E,6- 9 b]诱导抗病毒T细胞和抗体应答。此外,E-缺失的病毒在通过组织培养细胞盲传16次后是稳定的,仅检测到表面糖蛋白中的单一突变。传代病毒在小鼠中保持无毒力。这些结果表明,rSARS-CoV-ΔE是一种有效的候选疫苗,如果SARS复发,可能会有用。
The severe acute respiratory syndrome coronavirus (SARS-CoV) caused substantial morbidity and mortality in 2002–2003. Deletion of the envelope (E) protein modestly diminished virus growth in tissue culture but abrogated virulence in animals. Here, we show that immunization with rSARS-CoV-ΔE or SARS-CoV-Δ[E,6-9b] (deleted in accessory proteins (6, 7a, 7b, 8a, 8b, 9b) in addition to E) nearly completely protected BALB/c mice from fatal respiratory disease caused by mouse-adapted SARS-CoV and partly protected hACE2 Tg mice from lethal disease. hACE2 Tg mice, which express the human SARS-CoV receptor, are extremely susceptible to infection. We also show that rSARS-CoV-ΔE and rSARS-CoV-Δ[E,6-9b] induced anti-virus T cell and antibody responses. Further, the E-deleted viruses were stable after 16 blind passages through tissue culture cells, with only a single mutation in the surface glycoprotein detected. The passaged virus remained avirulent in mice. These results suggest that rSARS-CoV-ΔE is an efficacious vaccine candidate that might be useful if SARS recurred.
杆状病毒表达的SARS-COV膜蛋白加速了昆虫细胞中凋亡的诱导。
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