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实验性减毒活人副流感病毒 2 型疫苗在体外人纤毛气道上皮中的生长受限与在非洲绿猴中的减毒作用相平行。

Growth restriction of an experimental live attenuated human parainfluenza virus type 2 vaccine in human ciliated airway epithelium in vitro parallels attenuation in African green monkeys.

机构信息

Laboratory of Infectious Diseases, RNA Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-2007, USA.

出版信息

Vaccine. 2010 Mar 24;28(15):2788-98. doi: 10.1016/j.vaccine.2010.01.050. Epub 2010 Feb 20.


DOI:10.1016/j.vaccine.2010.01.050
PMID:20139039
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2844349/
Abstract

Human parainfluenza viruses (HPIVs) are common causes of severe pediatric respiratory viral disease. We characterized wild-type HPIV2 infection in an in vitro model of human airway epithelium (HAE) and found that the virus replicates to high titer, sheds apically, targets ciliated cells, and induces minimal cytopathology. Replication of an experimental, live attenuated HPIV2 vaccine strain, containing both temperature sensitive (ts) and non-ts attenuating mutations, was restricted >30-fold compared to rHPIV2-WT in HAE at 32 degrees C and exhibited little productive replication at 37 degrees C. This restriction paralleled attenuation in the upper and lower respiratory tract of African green monkeys, supporting the HAE model as an appropriate and convenient system for characterizing HPIV2 vaccine candidates.

摘要

人副流感病毒(HPIVs)是引起严重小儿呼吸道病毒病的常见原因。我们对人类气道上皮(HAE)体外模型中的野生型 HPIV2 感染进行了特征描述,发现该病毒可高效复制,呈顶端释放,靶向纤毛细胞,并引起最小的细胞病变。与 rHPIV2-WT 相比,含有温度敏感(ts)和非 ts 减毒突变的实验性减毒活 HPIV2 疫苗株在 32°C 的 HAE 中复制受到 >30 倍的限制,在 37°C 时几乎没有有效复制。这种限制与非洲绿猴上呼吸道和下呼吸道的衰减相平行,支持 HAE 模型作为一种合适且方便的系统,用于鉴定 HPIV2 疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/ee510c18c201/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/2cd813589959/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/d549db43d764/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/b8932edd43d7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/7cd8142d3baa/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/090c1775a2a3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/ee510c18c201/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/2cd813589959/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/d549db43d764/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/b8932edd43d7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/7cd8142d3baa/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/090c1775a2a3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac8/7126223/ee510c18c201/gr6.jpg

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本文引用的文献

[1]
Human parainfluenza virus type 2 V protein inhibits interferon production and signaling and is required for replication in non-human primates.

Virology. 2009-12-7

[2]
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PLoS Biol. 2009-7

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Avian Influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways.

PLoS Pathog. 2009-5

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Pediatr Infect Dis J. 2009-5

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J Pediatr. 2009-5

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Human parainfluenza virus type 1 C proteins are nonessential proteins that inhibit the host interferon and apoptotic responses and are required for efficient replication in nonhuman primates.

J Virol. 2008-9

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Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed.

J Clin Invest. 2008-7

[8]
Role of interferon in the replication of human parainfluenza virus type 1 wild type and mutant viruses in human ciliated airway epithelium.

J Virol. 2008-8

[9]
Select paramyxoviral V proteins inhibit IRF3 activation by acting as alternative substrates for inhibitor of kappaB kinase epsilon (IKKe)/TBK1.

J Biol Chem. 2008-5-23

[10]
The pathology of influenza virus infections.

Annu Rev Pathol. 2008

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