Abstract
The distribution of JC virus (JCV) variants in the brain, lung, liver, kidney, spleen and lymph nodes collected at autopsy from AIDS patients with (Group A: 10 Ss) and without (Group B: 5 Ss) progressive multifocal leukoencephalopathy (PML) and from HIV-negative patients (Group C: 5 Ss), was examined by amplifying the JCV large T antigen (LT), the regulatory (R) and the VP1 regions. Among the samples from the PML patients, JCV DNA was detected in all of the demyelinating areas, in 60% of the lesion-free brain tissues, in 60% of the lung tissues and in 40% of the spleen and kidney tissues, whereas all liver and lymph node sections were negative. JCV DNA was also found in two of the five brain specimens, in two of the five kidney specimens, in one of the five lung specimens from the HIV-positive patients without PML and in the brain specimens from two of the five HIV-negative subjects. Nucleotide sequence analysis indicated that all of the R region amplified from extraneural tissues had rearrangements similar to those of the Mad-4 strain and that VP1-region amplified products were similar to the Mad-1 strain. In the brain specimens from two PML patients, we found a unique rearranged R region, along with a VP1 region of JCV type 2. In addition, an almost unique variant with multiple rearrangements in the R region and unusual base mutations in the VP1 region was detected in the brain sample from another PML patient. The data indicate that diffuse visceral involvement of JCV is particularly frequent in AIDS patients with PML. Moreover, the presence of rearrangements and mutations, involving different regions of the viral genome, observed in PML-affected brain tissues, could represent a risk factor for the development of PML in immunosuppressed individuals.