Sequence analysis of the JC virus transcriptional control region detected in urine from HIV-positive patients.
OBJECTIVE
To investigate the correlation between transcriptional control region (TCR) types and virus replication and the role of decreased host immunity in inducing TCR changes.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Omodeo-Zorini
Elisabetta
E
Department of Medical Sciences, Faculty of Medicine and Surgery, University of East Piedmont Amedeo Avogadro.
Boldorini
Renzo
R
Viganò
Paolo
P
Mena
Maurizio
M
Benigni
Elisabetta
E
Andorno
Silvano
S
Monga
Guido
G
D001483:Base Sequence / Q000235:genetics; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000235:genetics / Q000652:urine*; D005809:Genes, Regulator / Q000235:genetics*; D016679:Genome, Viral; D015658:HIV Infections / Q000276:immunology / Q000652:urine / Q000821:virology*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology; D007577:JC Virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D017354:Point Mutation / Q000235:genetics; D014556:Urine / Q000821:virology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
D004279:DNA, Viral