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A single case observation: Is the Ebola virus soluble glycoprotein an indicator of viral recrudescence?

ABSTRACT: This case study investigated the long-term expression dynamics of Ebola virus (EBOV) soluble glycoprotein (sGP) in the serum of a patient who got infected with EBOV in West Africa and recovered from the acute Ebola virus disease (EVD) at the National Institutes of Health Clinical Center in Bethesda, MD, USA. Samples from this patient were collected during acute EVD and during convalescence up to day 361 following illness onset. While blood samples were negative by RT-qPCR after recovery from acute EVD, we detected small amounts of EBOV sGP in the serum of the patient long after recovery potentially indicating viral recrudescence. As this is only observed in a single patient, additional longitudinal patient samples are needed to confirm our hypothesis that EBOV sGP may be an indicator of viral recrudescence long after recovery from acute EVD.

SUBMITTER: Furuyama W

PROVIDER: S-EPMC10651190 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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A Single Case Observation: Is the Ebola Virus Soluble Glycoprotein an Indicator of Viral Recrudescence?

Furuyama Wakako W Davey Richard T RT Chertow Daniel S DS Marzi Andrea A

The Journal of infectious diseases 20231101 Suppl 7

This case study investigated the long-term expression dynamics of Ebola virus (EBOV) soluble glycoprotein (sGP) in the serum of a patient who was infected with EBOV in West Africa and recovered from acute Ebola virus disease (EVD) at the National Institutes of Health Clinical Center in Bethesda, Maryland. Samples from this patient were collected during acute EVD and during convalescence up to day 361 following illness onset. Although blood samples were negative by reverse transcription-quantitat ...[more]

PMID: 37474251

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Project description:BackgroundA key advantage of recombinant antibody technology is the ability to optimize and tailor reagents. Single domain antibodies (sdAbs), the recombinantly produced variable domains derived from camelid and shark heavy chain antibodies, provide advantages of stability and solubility and can be further engineered to enhance their properties. In this study, we generated sdAbs specific for Ebola virus envelope glycoprotein (GP) and increased their stability to expand their utility for use in austere locals. Ebola virus is extremely virulent and causes fatal hemorrhagic fever in ~ 50 percent of the cases. The viral GP binds to host cell receptors to facilitate viral entry and thus plays a critical role in pathogenicity.ResultsAn immune phage display library containing more than 107 unique clones was developed from a llama immunized with a combination of killed Ebola virus and recombinantly produced GP. We panned the library to obtain GP binding sdAbs and isolated sdAbs from 5 distinct sequence families. Three GP binders with dissociation constants ranging from ~ 2 to 20 nM, and melting temperatures from ~ 57 to 72 °C were selected for protein engineering in order to increase their stability through a combination of consensus sequence mutagenesis and the addition of a non-canonical disulfide bond. These changes served to increase the melting temperatures of the sdAbs by 15-17 °C. In addition, fusion of a short positively charged tail to the C-terminus which provided ideal sites for the chemical modification of these sdAbs resulted in improved limits of detection of GP and Ebola virus like particles while serving as tracer antibodies.ConclusionsSdAbs specific for Ebola GP were selected and their stability and functionality were improved utilizing protein engineering. Thermal stability of antibody reagents may be of particular importance when operating in austere locations that lack reliable refrigeration. Future efforts can evaluate the potential of these isolated sdAbs as candidates for diagnostic or therapeutic applications for Ebola.

Dataset Information

A single case observation: Is the Ebola virus soluble glycoprotein an indicator of viral recrudescence?

Publications

A Single Case Observation: Is the Ebola Virus Soluble Glycoprotein an Indicator of Viral Recrudescence?

Similar Datasets

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