Quantification of Viral and Host Biomarkers in the Liver of Rhesus Macaques A Longitudinal Study of Zaire Ebolavirus Strain Kikwit (EBOV/Kik)

被引：15

作者：

Greenberg, Alexandra ^{[1
]}

Huber, Bertrand R. ^{[2
]}

Liu, David X. ^{[5
]}

Logue, James P. ^{[5
]}

Hischak, Amanda M. W. ^{[5
]}

Hart, Randy J. ^{[5
]}

Abbott, Maureen ^{[5
]}

Isic, Nejra ^{[5
]}

Hisada, Yohei M. ^{[6
]}

Mackman, Nigel ^{[6
]}

Bennett, Richard S. ^{[5
]}

Hensley, Lisa E. ^{[5
]}

Connor, John H. ^{[3
]}

Crossland, Nicholas A. ^{[4
]}

机构：

[1] Boston Univ, Grad Med Sci, Sch Med, Boston, MA 02118 USA

[2] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02118 USA

[3] Boston Univ, Dept Med, Sch Med, Boston, MA 02118 USA

[4] Boston Univ, Dept Pathol & Lab Med, Sch Med, 620 Albany St,401R, Boston, MA 02118 USA

[5] NIAID, Integrated Res Facil, Frederick, MD USA

[6] Univ N Carolina, Div Hematol & Oncol, Dept Med, Chapel Hill, NC 27515 USA

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2020年 / 190卷 / 07期

关键词：

HEMORRHAGIC-FEVER; TISSUE FACTOR; VIRUS; PATHOGENESIS; ACTIVATION; MARBURG;

D O I：

10.1016/j.ajpath.2020.03.003

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Zaire ebolavirus (EBOV) causes Ebola virus disease (EVD), which carries a fatality rate between 25% and 90% in humans. Liver pathology is a hallmark of terminal EVD; however, little is known about temporal disease progression. We used multiplexed fluorescent immunohistochemistry and in situ hybridization in combination with whole slide imaging and image analysis (IA) to quantitatively characterize temporospatial signatures of viral and host factors as related to EBOV pathogenesis. Eighteen rhesus monkeys euthanized between 3 and 8 days post-infection, and 3 uninfected controls were enrolled in this study. Compared with semiquantitative histomorphologic ordinal scoring, quantitative IA detected subtle and progressive features of early and terminal EVD that was not feasible with routine approaches. Sinusoidal macrophages were the earliest cells to respond to infection, expressing proinflammatory cytokine interleukin 6 (IL6) mRNA, which was subsequently also observed in fibrovascular compartments. The mRNA of interferon-stimulated gene-15 (ISG-15), also known as ISG15 ubiquitin like modifier (ISG15), was observed early, with a progressive and ubiquitous hybridization signature involving mesenchymal and epithelial compartments. ISG-15 mRNA was prominent near infected cells, but not in infected cells, supporting the hypothesis that bystander cells produce a robust interferon gene response. This study contributes to our current understanding of early EVD progression and illustrates the value that digital pathology and quantitative IA serve in infectious disease research.

引用

页码：1449 / 1460

页数：12