Synthetic antibodies and peptides recognizing progressive multifocal leukoencephalopathy-specific point mutations in polyomavirus JC capsid viral protein 1.

TitleSynthetic antibodies and peptides recognizing progressive multifocal leukoencephalopathy-specific point mutations in polyomavirus JC capsid viral protein 1.
Publication TypeJournal Article
Year of Publication2015
AuthorsChen, Gang, Gorelik Leonid, Simon Kenneth J., Pavlenco Alevtina, Cheung Anne, Brickelmaier Margot, Chen Ling Ling, Jin Ping, Weinreb Paul H., and Sidhu Sachdev S.
JournalMAbs
Volume7
Issue4
Pagination681-92
Date Published2015
ISSN1942-0870
KeywordsCapsid Proteins, Humans, JC Virus, Leukoencephalopathy, Progressive Multifocal, Mutation, Peptides, Single-Chain Antibodies
Abstract

<p>Polyomavirus JC (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal brain disease that afflicts a small fraction of the immune-compromised population, including those affected by AIDS and transplantation recipients on immunosuppressive drug therapy. Currently there is no specific therapy for PML. The major capsid viral protein 1 (VP1) involved in binding to sialic acid cell receptors is believed to be a key player in pathogenesis. PML-specific mutations in JCV VP1 sequences present at the binding pocket of sialic acid cell receptors, such as L55F and S269F, abolish sialic acid recognition and might favor PML onset. Early diagnosis of these PML-specific mutations may help identify patients at high risk of PML, thus reducing the risks associated with immunosuppressive therapy. As a first step in the development of such early diagnostic tools, we report identification and characterization of affinity reagents that specifically recognize PML-specific mutations in VP1 variants using phage display technology. We first identified 2 peptides targeting wild type VP1 with moderate specificity. Fine-tuning via selection of biased libraries designed based on 2 parental peptides yielded peptides with different, yet still moderate, bindinspecificities. In contrast, we had great success in identifying synthetic antibodies that recognize one of the PML-specific mutations (L55F) with high specificity from the phage-displayed libraries. These peptides and synthetic antibodies represent potential candidates for developing tailored immune-based assays for PML risk stratification in addition to complementing affinity reagents currently available for the study of PML and JCV.</p>

DOI10.1080/19420862.2015.1038447
Alternate JournalMAbs
PubMed ID25879139
PubMed Central IDPMC4623438

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