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Measurement of BK-polyomavirus Non-Coding Control Region Driven Transcriptional Activity Via Flow Cytometry
Published on: July 13, 2019
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.
Background:
JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy (PML), is classified in 8 different genotypes. Previous reports have suggested a positive association between specific genotypes and PML.
Objective:
To compare genotypes and adaptive mutations of JCV strains from Brazilian AIDS patients with and without PML.
Study Design:
The VP1 region of JCV was amplified by polymerase chain reaction from cerebrospinal fluid samples from 51 patients with PML and from urine samples of 47 patients with AIDS without central nervous system disease. Genotyping was done by phylogenetic analysis. Amino acid replacement and selection pressures were also investigated.
Results:
JCV genotype frequency distributions showed that genotypes 2 (32.7%), 1 (26.5%) and 3 (23.5%) were the most prevalent. Genotype 1 had a positive association (p<0.0001) and genotype 3 showed an inverse association (p<0.001) with PML. A previously undescribed point mutation at residue 91 (L/I or L/V) and (L/P), non-genotype-associated, was found in 5/49 (10.2%) and 2/47 (4.3%) JCV sequences from PML and non-PML patients, respectively. This mutation was under positive selection only in PML patients. A previously described substitution of T-A in position 128 showed a significant difference between PML and non-PML cases (70% versus 16%, respectively, p<0.0005).
Conclusion:
In Brazilian patients with AIDS, JCV genotype 1 showed a strong association with PML (p<0.0001) and JCV genotype 3 showed an inverse association with PML. The possible association of aminoacids substitution in residues 91 and 128 with PML in patients with AIDS must be further investigated.
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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