JC polyomavirus mutants escape antibody-mediated neutralization
| Autor: | Simonetta Gerevini, Upasana Ray, Paola Cinque, Diana V. Pastrana, Adriano Lazzarin, Valeria Longo, Roland Martin, Christopher B. Buck, Sven Schippling |
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| Přispěvatelé: | University of Zurich, Buck, C B |
| Rok vydání: | 2015 |
| Předmět: |
viruses
JC virus 610 Medicine & health 2700 General Medicine Biology medicine.disease_cause Neutralization Virus Article Serology Neutralization Tests medicine Humans Immune Evasion Viral Vaccine Progressive multifocal leukoencephalopathy virus diseases Viral Vaccines General Medicine medicine.disease Virology JC Virus 10040 Clinic for Neurology nervous system diseases Vaccination nervous system Immunology Humoral immunity Mutation |
| DOI: | 10.5167/uzh-115468 |
| Popis: | JC polyomavirus (JCV) persistently infects the urinary tract of a majority of adults. Under conditions of immune impairment, JCV causes an opportunistic brain disease, progressive multifocal leukoencephalopathy (PML). JCV strains found in the cerebrospinal fluid (CSF) of PML patients contain distinctive mutations in surface loops of the major capsid protein, VP1. We hypothesized that VP1 mutations might allow the virus to evade antibody-mediated neutralization. Consistent with this hypothesis, neutralization serology revealed that plasma samples from PML patients neutralized wild-type JCV strains but failed to neutralize patient-cognate PML-mutant JCV strains. This contrasted with serological results for healthy individuals, most of whom robustly cross-neutralized all tested JCV variants. Mice administered a JCV virus-like particle (VLP) vaccine initially showed neutralizing “blind spots” (akin to those observed in PML patients) that closed after booster immunization. A PML patient administered an experimental JCV VLP vaccine likewise showed dramatically increased neutralizing titer against her cognate PML-mutant JCV. The results indicate that deficient humoral immunity is a common aspect of PML pathogenesis and that vaccination may overcome this humoral deficiency. Thus, vaccination with JCV VLPs might prevent the development of PML. |
| Databáze: | OpenAIRE |
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