Ebola Virus Genome Plasticity as a Marker of Its Passaging History: A Comparison of In Vitro Passaging to Non-Human Primate Infection

被引：38

作者：

Kugelman, Jeffrey R. ^{[1
]}

Lee, Michael S. ^{[1
,6
]}

Rossi, Cynthia A. ^{[4
]}

McCarthy, Sarah E. ^{[1
]}

Radoshitzky, Sheli R. ^{[3
]}

Dye, John M. ^{[2
]}

Hensley, Lisa E. ^{[2
]}

Honko, Anna ^{[2
]}

Kuhn, Jens H. ^{[5
]}

Jahrling, Peter B. ^{[5
]}

Warren, Travis K. ^{[3
]}

Whitehouse, Chris A. ^{[1
]}

Bavari, Sina ^{[3
]}

Palacios, Gustavo ^{[1
]}

机构：

[1] USAMRIID, Genom Div, Ft Detrick, MD USA

[2] USAMRIID, Div Virol, Ft Detrick, MD USA

[3] USAMRIID, Div Toxicol, Ft Detrick, MD USA

[4] USAMRIID, Diagnost Syst Div, Ft Detrick, MD USA

[5] NIAID, Integrated Res Facil Ft Detrick, NIH, Ft Detrick, MD USA

[6] USA, Simulat Sci Branch, Res Lab, Aberdeen Proving Ground, MD USA

来源：

PLOS ONE | 2012年 / 7卷 / 11期

关键词：

VIRION GLYCOPROTEINS; HEMORRHAGIC-FEVER; ZAIRE EBOLAVIRUS; RNA; RECEPTOR;

D O I：

10.1371/journal.pone.0050316

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

To identify polymorphic sites that could be used as biomarkers of Ebola virus passage history, we repeatedly amplified Ebola virus (Kikwit variant) in vitro and in vivo and performed deep sequencing analysis of the complete genomes of the viral subpopulations. We then determined the sites undergoing selection during passage in Vero E6 cells. Four locations within the Ebola virus Kikwit genome were identified that together segregate cell culture-passaged virus and virus obtained from infected non-human primates. Three of the identified sites are located within the glycoprotein gene (GP) sequence: the poly-U (RNA editing) site at position 6925, as well as positions 6677, and 6179. One site was found in the VP24 gene at position 10833. In all cases, in vitro and in vivo, both populations (majority and minority variants) were maintained in the viral swarm, with rapid selections occurring after a few passages or infections. This analysis approach will be useful to differentiate whether filovirus stocks with unknown history have been passaged in cell culture and may support filovirus stock standardization for medical countermeasure development.

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