Molecular characterization of human polyomavirus JC in Brazilian AIDS patients with and without progressive

Maria Cristina Domingues Fink1, Augusto Cesar Penalva de Oliveira, Camila Malta Romano

  • 1Universidade de São Paulo, Instituto de Medicina Tropical de São Paulo, Avenida Dr. Eneas de Carvalho Aguiar 470, São Paulo, Brazil.

Abstract

Insights

JC virus (JCV) genotype 1 is strongly associated with progressive multifocal leukoencephalopathy (PML) in Brazilian AIDS patients, while genotype 3 shows an inverse association. Further research is needed on specific mutations

Area of Science:

  • Virology
  • Immunology
  • Epidemiology

Background:

  • JC virus (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML).
  • JCV is classified into 8 genotypes, with some genotypes previously linked to PML.
  • Understanding JCV genotype distribution and its association with PML in specific populations is crucial.

Purpose of the Study:

  • To compare genotypes and adaptive mutations of JCV strains in Brazilian AIDS patients with and without PML.
  • To investigate the association between specific JCV genotypes and the development of PML in this cohort.
  • To identify potential novel mutations or variations in JCV associated with PML.

Main Methods:

  • Polymerase chain reaction (PCR) was used to amplify the VP1 region of JCV from patient samples (CSF for PML, urine for non-PML).
  • Phylogenetic analysis was employed for JCV genotyping.
  • Amino acid substitutions and selection pressures were analyzed to identify adaptive mutations.

Main Results:

  • JCV genotypes 2, 1, and 3 were the most prevalent in the study population.
  • JCV genotype 1 showed a significant positive association with PML (p<0.0001).
  • JCV genotype 3 exhibited a significant inverse association with PML (p<0.001).
  • A novel mutation at residue 91 was found in PML patients and was under positive selection.
  • A substitution at position 128 (T-A) was significantly more frequent in PML cases.

Conclusions:

  • JCV genotype 1 is strongly associated with PML in Brazilian AIDS patients.
  • JCV genotype 3 demonstrates an inverse association with PML in this population.
  • The role of amino acid substitutions at residues 91 and 128 in PML pathogenesis warrants further investigation.

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