Sequence Analysis of the JC Virus Transcriptional Control Region Detected in Urine from HIV-Positive Patients

Abstract

To investigate the correlation between transcriptional control region (TCR) types and virus replication and the role of decreased host immunity in inducing TCR changes. In a previous study, urine specimens from 78 unselected HIV-positive patients were independently evaluated by cytology, immunohistochemistry and nested polymerase chain reaction (n-PCR) to detect the presence of polyomaviruses. The JC virus (JCV) large T region was positive in 44/78 (56%) urine specimens by n-PCR. In the current study, these cases further underwent to n-PCR to detect TCR, and the amplified products were sequenced. The JCV types identified were compared using: (1) morphologic evidence of replication (decoy cells and/or immunohistochemical staining of cells detected using anti-SV 40 antiserum), and (2) patients' immune status (CD4+ cell counts). TCR was successfully amplified in 30/44 cases (68%). TCR sequence analysis disclosed 6/30 archetype (20%) and 24/30 archetypelike sequences, the latter distributed as follows: 4 G2 (4/30, 13%) with G-->A substitutions in the C sequence (nt 9), and 20 CY (20/30, 67%) with A-->G substitutions in the F sequence (nt 19). There were no correlations with morphologic evidence of viral replication or immune status. The present study indicated that TCR in urine samples from PML-free HIV-positive subjects are archetypes or archetypelike. Immune suppression does not seem to influence minor changes in the TCR genome, and single by mutations do not change JCV replication activity.