Novel mass spectrometry based detection and identification of variants of rabies virus nucleoprotein in infected brain tissues.

Human rabies is an encephalitic disease transmitted by animals infected with lyssaviruses. The most common lyssavirus that causes human infection is rabies virus (RABV), the prototypic member of the genus. The incubation period of RABV in humans varies from few weeks to several months in some instan...

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Main Authors: Matthew Reed, Olga Stuchlik, William C Carson, Lillian Orciari, Pamela A Yager, Victoria Olson, Yu Li, Xianfu Wu, Jan Pohl, Panayampalli Subbian Satheshkumar
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-12-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://doi.org/10.1371/journal.pntd.0006984
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author Matthew Reed
Olga Stuchlik
William C Carson
Lillian Orciari
Pamela A Yager
Victoria Olson
Yu Li
Xianfu Wu
Jan Pohl
Panayampalli Subbian Satheshkumar
author_facet Matthew Reed
Olga Stuchlik
William C Carson
Lillian Orciari
Pamela A Yager
Victoria Olson
Yu Li
Xianfu Wu
Jan Pohl
Panayampalli Subbian Satheshkumar
author_sort Matthew Reed
collection DOAJ
description Human rabies is an encephalitic disease transmitted by animals infected with lyssaviruses. The most common lyssavirus that causes human infection is rabies virus (RABV), the prototypic member of the genus. The incubation period of RABV in humans varies from few weeks to several months in some instances. During this prodromal period, neither antibodies nor virus is detected. Antibodies, antigen and nucleic acids are detectable only after the onset of encephalitic symptoms, at which point the outcome of the disease is nearly 100% fatal. Hence, the primary intervention for human RABV exposure and subsequent post-exposure prophylaxis relies on testing animals suspected of having rabies. The most widely used diagnostic tests in animals focus on antigen detection, RABV-encoded nucleoprotein (N protein) in brain tissues. N protein accumulates in the cytoplasm of infected cells as large and granular inclusions, which are visualized in infected brain tissues by immuno-microscopy using anti-N protein antibodies. In this study, we explored a mass spectrometry (MS) based method for N protein detection without the need for any specific antibody reagents or microscopy. The MS-based method described here is unbiased, label-free, requires no amplification and determines any previously sequenced N protein available in the database. The results demonstrate the ability of MS/MS based method for N protein detection and amino acid sequence determination in animal diagnostic samples to obtain RABV variant information. This study demonstrates a potential for future developments of rabies diagnostic tests based on MS platforms.
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spelling doaj.art-652b2626867d46958d7636fae6c9e2d72022-12-21T19:11:15ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352018-12-011212e000698410.1371/journal.pntd.0006984Novel mass spectrometry based detection and identification of variants of rabies virus nucleoprotein in infected brain tissues.Matthew ReedOlga StuchlikWilliam C CarsonLillian OrciariPamela A YagerVictoria OlsonYu LiXianfu WuJan PohlPanayampalli Subbian SatheshkumarHuman rabies is an encephalitic disease transmitted by animals infected with lyssaviruses. The most common lyssavirus that causes human infection is rabies virus (RABV), the prototypic member of the genus. The incubation period of RABV in humans varies from few weeks to several months in some instances. During this prodromal period, neither antibodies nor virus is detected. Antibodies, antigen and nucleic acids are detectable only after the onset of encephalitic symptoms, at which point the outcome of the disease is nearly 100% fatal. Hence, the primary intervention for human RABV exposure and subsequent post-exposure prophylaxis relies on testing animals suspected of having rabies. The most widely used diagnostic tests in animals focus on antigen detection, RABV-encoded nucleoprotein (N protein) in brain tissues. N protein accumulates in the cytoplasm of infected cells as large and granular inclusions, which are visualized in infected brain tissues by immuno-microscopy using anti-N protein antibodies. In this study, we explored a mass spectrometry (MS) based method for N protein detection without the need for any specific antibody reagents or microscopy. The MS-based method described here is unbiased, label-free, requires no amplification and determines any previously sequenced N protein available in the database. The results demonstrate the ability of MS/MS based method for N protein detection and amino acid sequence determination in animal diagnostic samples to obtain RABV variant information. This study demonstrates a potential for future developments of rabies diagnostic tests based on MS platforms.https://doi.org/10.1371/journal.pntd.0006984
spellingShingle Matthew Reed
Olga Stuchlik
William C Carson
Lillian Orciari
Pamela A Yager
Victoria Olson
Yu Li
Xianfu Wu
Jan Pohl
Panayampalli Subbian Satheshkumar
Novel mass spectrometry based detection and identification of variants of rabies virus nucleoprotein in infected brain tissues.
PLoS Neglected Tropical Diseases
title Novel mass spectrometry based detection and identification of variants of rabies virus nucleoprotein in infected brain tissues.
title_full Novel mass spectrometry based detection and identification of variants of rabies virus nucleoprotein in infected brain tissues.
title_fullStr Novel mass spectrometry based detection and identification of variants of rabies virus nucleoprotein in infected brain tissues.
title_full_unstemmed Novel mass spectrometry based detection and identification of variants of rabies virus nucleoprotein in infected brain tissues.
title_short Novel mass spectrometry based detection and identification of variants of rabies virus nucleoprotein in infected brain tissues.
title_sort novel mass spectrometry based detection and identification of variants of rabies virus nucleoprotein in infected brain tissues
url https://doi.org/10.1371/journal.pntd.0006984
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