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JC virus genotypes in France: molecular epidemiology and potential significance for progressive multifocal
Abstract:
JC virus (JCV) induces progressive multifocal leukoencephalopathy (PML), especially in human immunodeficiency virus (HIV)-infected patients. Although JCV genotypes have primarily been associated with geographic patterns, a distinctive neuropathogenicity was recently attributed to genotype 2. A multicenter study was conducted to describe the distribution of JCV genotypes in France and to investigate correlations between genotypes and PML. Genotypes were determined by sequencing 494 bp in the VP1 capsid gene. Peripheral JCV was studied in 65 urine samples from 43 HIV-infected patients and from 22 control subjects. Genotypes 1, 4, 2, and 3 were detected in 52.3%, 30.8%, 12.3%, and 4.6% of the samples, respectively. In 56 brain or cerebrospinal fluid samples, PML-associated JCV of genotypes 1, 2, 4, and 3 was found in 66%, 19.7%, 8.9%, and 5.4%, respectively. Infection with JCV genotypes 1 or 2 was correlated with PML (odds ratio, 3.29). On the other hand, infection with JCV genotype 4 could represent a lower risk for PML.
Insights
John Cunningham virus (JCV) genotypes 1 and 2 are linked to progressive multifocal leukoencephalopathy (PML) in HIV patients. Genotype 4 may indicate a reduced risk for developing PML.
Area of Science:
- Neurovirology
- Infectious Diseases
- Genetics
Background:
- John Cunningham virus (JCV) is a polyomavirus that can cause progressive multifocal leukoencephalopathy (PML).
- PML is a serious opportunistic infection, particularly affecting individuals with compromised immune systems, such as those with human immunodeficiency virus (HIV).
- While JCV genotypes are often linked to geographical distribution, recent findings suggest a potential link between specific genotypes and neuropathogenicity.
Purpose of the Study:
- To determine the distribution of JCV genotypes in France.
- To investigate the association between different JCV genotypes and the occurrence of PML.
- To assess the neuropathogenic potential of distinct JCV genotypes in relation to PML development.
Main Methods:
- A multicenter study involving the sequencing of the VP1 capsid gene (494 bp) to identify JCV genotypes.
- Analysis of peripheral JCV in urine samples from 43 HIV-infected patients and 22 control subjects.
- Examination of JCV genotypes in brain or cerebrospinal fluid samples from 56 patients with PML.
Main Results:
- JCV genotypes 1, 4, 2, and 3 were detected in peripheral samples at frequencies of 52.3%, 30.8%, 12.3%, and 4.6%, respectively.
- In PML cases, JCV genotypes 1, 2, 4, and 3 were identified in 66%, 19.7%, 8.9%, and 5.4% of samples, respectively.
- Infection with JCV genotypes 1 or 2 showed a significant correlation with PML (odds ratio, 3.29), while genotype 4 appeared to be associated with a lower risk.
Conclusions:
- JCV genotype distribution in France shows a predominance of genotype 1.
- JCV genotypes 1 and 2 are significantly associated with the development of PML in the studied population.
- JCV genotype 4 may represent a lower risk factor for PML, warranting further investigation into genotype-specific neuropathogenicity.
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