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Original article| Volume 56, 103266, November 2021

Mutations in the John Cunningham virus VP1 gene could predispose to the development of progressive multifocal leukoencephalopathy in multiple sclerosis patients undergoing treatment with natalizumab

Published:September 14, 2021DOI:https://doi.org/10.1016/j.msard.2021.103266
Mutations in the John Cunningham virus VP1 gene could predispose to the development of progressive multifocal leukoencephalopathy in multiple sclerosis patients undergoing treatment with natalizumab
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      Highlights

      • •
        Treatment with NTZ is at risk of developing PML.
      • •
        There is no correlation between anti-JC virus antibody index and JC virus DNA.
      • •
        JC virus mutations in VP1 gene provide predictive information for PML development.
      • •
        The identify the genotype of JC virus allows more efficient treatment and follow-up .

      Abstract

      Background

      Patients with Multiple Sclerosis (MS) undergoing treatment with natalizumab (NTZ) are at risk of developing progressive multifocal leukoencephalopathy (PML) due to the reactivation of John Cunningham (JC) virus. A relevant characteristic among PML cases is the development of single nucleotide mutations in the VP1 gene of the causal JC virus. The identification of such mutations in timely manner can provide valuable information for MS management.

      Objective

      To identify mutations along the JC virus VP1 gene in MS patients undergoing treatment with NTZ, and correlate them with anti-JC virus antibody index.

      Methods

      Eighty-eight MS patients, one hundred twenty controls, and six patients with diagnosis of Human Immunodeficiency Virus (HIV) with and without secondary PML were included. JC virus was identified in peripheral blood mononuclear cells and cerebrospinal fluid by PCR. Amplification and sequencing of the entire length of the VP1 gene were performed in all positive clinical samples.

      Results

      In MS cases no mutations were observed in the JC virus VP1 gene, but it was positive in HIV controls with PML. Interestingly, the JC virus VP1 gene sequence derived from the HIV patients exhibited a non-silent substitution in position 186 (G → C), leading to an amino acid change (Lys → Asp). We did not find correlation between anti-JC virus antibody index and DNA viral detection.

      Conclusions

      . The identification of single nucleotide mutants in the JC virus VP1 gene might be an early predictive marker to PML for efficient patient treatment and follow-up.

      Keywords

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      Article info

      Publication history

      Published online: September 14, 2021
      Accepted: September 13, 2021
      Received in revised form: September 9, 2021
      Received: July 21, 2021

      Identification

      DOI: https://doi.org/10.1016/j.msard.2021.103266

      Copyright

      © 2021 Elsevier B.V. All rights reserved.

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