專訪：歐洲病毒學專家 董宇紅博士

【縛雞之見】

基因或生物科技研究時道德？

道德？我沒聽錯吧！

這正好是中國共產黨，甚至於，是現代中國文化所欠缺的特質。

Engineered bat virus stirs debate over risky research    Declan Butler＠NATURE 20151112

Lab-made coronavirus related to SARS can infect human cells.

A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence    Letter by VD Menachery to Nature Medicine  20151109

Abstract

嚴重急性呼吸系統綜合症冠狀病毒（SARS-CoV）和中東呼吸系統綜合症（MERS）-CoV的出現突顯了跨物種傳播事件的威脅，導致人類暴發。在這裡，我們檢查了目前在中國馬蹄蝠種群中傳播的SARS樣病毒SHC014-CoV的潛在疾病。使用SARS-CoV反向遺傳學系統，我們生成並鑑定了一種嵌合病毒，該病毒在適應小鼠的SARS-CoV主幹中表達蝙蝠冠狀病毒SHC014的尖峰。結果表明，在野生型主鏈中編碼SHC014刺突的2b組病毒可以有效利用SARS受體人類血管緊張素轉化酶II（ACE2）的多個直系同源物，在原代人氣道細胞中有效複製，並達到與流行病相當的體外滴度SARS-CoV株。另外，體內實驗證明嵌合病毒在小鼠肺中的複制具有明顯的發病機理。對可用的基於SARS的免疫治療和預防方式的評估顯示療效較差；單複製抗體和疫苗方法均無法使用新型刺突蛋白中和並防止CoV感染。基於這些發現，我們合成了感染性全長SHC014重組病毒，並在體外和體內證明了強大的病毒複製能力。我們的工作表明，蝙蝠種群中目前流行的病毒可能會再次出現SARS-CoV的潛在風險。

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.