Evidence map›Paper›PMID 32194356›Full record

ArticleClinical proteomics2020

Early detection of Ebola virus proteins in peripheral blood mononuclear cells from infected mice.

Michael D Ward, Tara Kenny, Ernie Bruggeman, Christopher D Kane, Courtney L Morrell, Molly M Kane, Sandra Bixler, Sarah L Grady, Rachel S Quizon, Mekbib Astatke and 1 more

Abstract read
In one paragraph

Article in Clinical proteomics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Michael D Ward1Systems and Stuctural Biology Division, Protein Sciences Branch, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD USA.
Tara Kenny1Systems and Stuctural Biology Division, Protein Sciences Branch, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD USA.
Ernie Bruggeman1Systems and Stuctural Biology Division, Protein Sciences Branch, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD USA.
Christopher D Kane2Therapeutic Development Center, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD USA.
Courtney L Morrell1Systems and Stuctural Biology Division, Protein Sciences Branch, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD USA.
Molly M Kane2Therapeutic Development Center, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD USA.
Sandra Bixler2Therapeutic Development Center, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD USA.
Sarah L Grady3Applied Biological Sciences, The Johns Hopkins University Applied Physics Laboratory, 11100 Johns Hopkins Road, Laurel, MD USA.
Rachel S Quizon3Applied Biological Sciences, The Johns Hopkins University Applied Physics Laboratory, 11100 Johns Hopkins Road, Laurel, MD USA.
Mekbib Astatke3Applied Biological Sciences, The Johns Hopkins University Applied Physics Laboratory, 11100 Johns Hopkins Road, Laurel, MD USA.
Lisa H Cazares1Systems and Stuctural Biology Division, Protein Sciences Branch, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD USA.ORCID 0000-0001-5754-6192

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDetection of viral ribo-nucleic acid (RNA) via real-time polymerase chain reaction (RT-PCR) is the gold standard for the detection of Ebola virus (EBOV) during acute infection. However, the earliest window for viral RNA detection in blood samples is 48-72 h post-onset of symptoms. Therefore, efforts to develop additional orthogonal assays using complementary immunological and serological technologies are still needed to provide simplified methodology for field diagnostics. Furthermore, unlike RT-PCR tests, immunoassays that target viral proteins and/or early host responses are less susceptible to sequence erosion due to viral genetic drift. Although virus is shed into the bloodstream from infected cells, the wide dynamic range of proteins in blood plasma makes this a difficult sample matrix for the detection of low-abundant viral proteins. We hypothesized that the isolation of peripheral blood mononuclear cells (PBMCs), which are the first cellular targets of the Ebola virus (EBOV), may provide an enriched source of viral proteins.

methodsA mouse infection model that employs a mouse-adapted EBOV (MaEBOV) was chosen as a proof-of-principal experimental paradigm to determine if viral proteins present in PBMCs can help diagnose EBOV infection pre-symptomatically. We employed a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) platform to provide both high sensitivity and specificity for the detection and relative quantitation of viral proteins in PBMCs collected during MaEBOV infection. Blood samples pooled from animals at the post-infection time-points were used to determine the viral load by RT-PCR and purify PBMCs.

resultsUsing quantitative LC-MS/MS, we detected two EBOV proteins (vp40 and nucleoprotein) in samples collected on Day 2 post-infection, which was also the first day of detectable viremia via RT-PCR. These results were confirmed via western blot which was performed on identical PBMC lysates from each post-infection time point.

conclusionsWhile mass spectrometry is not currently amenable to field diagnostics, these results suggest that viral protein enrichment in PBMCs in tandem with highly sensitive immunoassays platforms, could lead to the development of a rapid, high-throughput diagnostic platform for pre-symptomatic detection of EBOV infection.

Indexed as

DiagnosticsEbola virusMouse adapted Ebola virusQuantitative proteomics

Identifiers

PMID32194356
PMCPMC7077124

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.