Comparative analyses of small molecule and antibody inhibition on glycoprotein-mediated entry of Měnglà virus with other filoviruses.
Comparative analyses of small molecule and antibody inhibition on glycoprotein-mediated entry of Měnglà virus with other filoviruses.
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小分子和抗体抑制Minglà病毒与其他丝状病毒糖蛋白介导的进入的比较分析。
DOI：
10.1002/jmv.27739
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发表时间：
2022-07
影响因子：
12.7
通讯作者：
Rong, Lijun
中科院分区：
文献类型：
--
作者：
Cooper, Laura;Achi, Jazmin Galvan;Rong, Lijun
丝状病毒科病毒（埃博拉病毒[EBOV]和马尔堡病毒[MARV]）引发严重人类疾病的能力及其大流行的可能性，使得所有新出现的丝状病毒病原体都成为人类的关注点。最近在中国云南省勐腊县蝙蝠的肝脏中发现了属于新属滇罗病毒（Dianlovirus）的勐腊病毒（MLAV）。MLAV利用NPC1作为内体受体、转导哺乳动物细胞以及抑制干扰素反应的能力表明，这种潜在病原体可能导致人类疾病。尽管研究人员付出了巨大努力，但仅恢复了病毒基因组，活的MLAV分离未获成功。在此，我们利用一种携带MLAV糖蛋白（GP）的假病毒模型，研究了MLAV - GP对蛋白酶的依赖性，以及小分子和抗体抑制MLAV病毒进入的能力。与EBOV和MARV一样，MLAV - GP需要蛋白水解加工，但与MARV类似，它不依赖组织蛋白酶B的活性来实现病毒进入。此外，先前发现的小分子抑制剂和抗体是MLAV抑制剂，这表明开发这些抑制剂作为广谱丝状病毒抗病毒药物是有可能的。总体而言，该研究的结果证实MLAV病毒进入在生物学上是独特的，但与MARV有相似之处。
在我们的研究中，我们表明先前发现的小分子丝状病毒抑制剂也能抑制勐腊病毒（MLAV）的进入。
利用一种假病毒构建体，我们发现MLAV进入需要蛋白水解加工，但不依赖组织蛋白酶B。
这是第一项表明MLAV病毒进入在生物学上独特但与马尔堡病毒有相似之处的研究。
The ability of viruses in the Filoviridae family (Ebola virus [EBOV] and Marburg virus [MARV]) to cause severe human disease and their pandemic potential makes all emerging filoviral pathogens a concern to humanity. Měnglà virus (MLAV) belonging to the new genus Dianlovirus was recently discovered in the liver of bats from Měnglà County, Yunnan Province, China. The capacity of MLAV to utilize NPC1 as an endosomal receptor, to transduce mammalian cells, and suppress IFN response suggests that this potential pathogen could cause human illness. Despite great effort by researchers, only the viral genome has been recovered and isolation of live MLAV had been unsuccessful. Here using a pseudovirus model baring the MLAV glycoprotein (GP), we studied the protease dependence of the MLAV‐GP, and the ability of small molecules and antibodies to inhibit MLAV viral entry. Like EBOV and MARV, the MLAV‐GP requires proteolytic processing but like MARV it does not depend on cathepsin B activity for viral entry. Furthermore, previously discovered small‐molecule inhibitors and antibodies are MLAV inhibitors and show the possibility of developing these inhibitors as broad‐spectrum filovirus antivirals. Overall, the findings in the study confirmed that MLAV viral entry is biologically distinct but has similarities to MARV. In our study, we show that previously discovered small‐molecule filovirus inhibitors also inhibit Měnglà Virus (MLAV) entry. Using a pseudovirus construct, we found that MLAV requires proteolytic processing for entry but is not dependent on cathepsin B. This is the first study to show MLAV viral entry is biologically distinct but has similarities to Marburg Virus.
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影响因子：
3.7
作者：
Towner JS;Pourrut X;Albariño CG;Nkogue CN;Bird BH;Grard G;Ksiazek TG;Gonzalez JP;Nichol ST;Leroy EM
通讯作者：
Leroy EM
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：
3.7
作者：
Manicassamy, Balaji;Wang, Jizhen;Rong, Lijun
通讯作者：
Rong, Lijun
影响因子：
3.7
作者：
Gnirss K;Kühl A;Karsten C;Glowacka I;Bertram S;Kaup F;Hofmann H;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
17.1
作者：
Johansen LM;Brannan JM;Delos SE;Shoemaker CJ;Stossel A;Lear C;Hoffstrom BG;Dewald LE;Schornberg KL;Scully C;Lehár J;Hensley LE;White JM;Olinger GG
通讯作者：
Olinger GG