Investigation on the role of cell transcriptional factor Sp1 and HIV-1 TAT protein in PML onset or development.
JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), characterized by multiple areas of demyelination and attendant loss of brain function. PML is often associated with immunodepression and it is significantly frequent in AIDS patients. The viral genome is divided into early and late genes, between which lies a non-coding control region (NCCR) that regulates JCV replication and presents a great genetic variability. The NCCR of JCV archetype (CY strain) is divided into six regions: A-F containing binding sites for cell factors involved in viral transcription. Deletions and enhancements of these binding sites characterize JCV variants, which could promote viral gene expression and could be more suitable for the onset or development of PML. Therefore, we evaluated by means of polymerase chain reaction (PCR) the presence of JCV genome in cerebrospinal fluid (CSF) of HIV positive and negative subjects both with PML and after sequencing, we analyzed the viral variants found focusing on Sp1 binding sites (box B and D) and up-TAR sequence (box C). It is known that Sp1 activates JCV early promoter and can contribute in maintaining methylation-free CpG islands in active genes, while up-TAR sequence is important for HIV-1 Tat stimulation of JCV late promoter. Our results showed that in HIV-positive subjects all NCCR structures presented enhancements of up-TAR element, whereas in HIV-negative subjects both Sp1 binding sites were always retained. Therefore, we can support the synergism HIV-1/JCV in CNS and we can hypothesize that both Sp1 binding sites could be important to complete JCV replication cycle in absence of HIV-coinfection.
Mischitelli
M
M
Department of Public Health Sciences, University of Rome La Sapienza, Italy.
Fioriti
D
D
Videtta
M
M
Degener
A M
AM
Antinori
A
A
Cinque
P
P
Giordano
A
A
Pietropaolo
V
V
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence / Q000235:genetics; D018450:Disease Progression; D015696:Gene Products, tat / Q000378:metabolism*; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000134:cerebrospinal fluid / Q000150:complications / Q000378:metabolism / Q000821:virology; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000302:isolation & purification; D007968:Leukoencephalopathy, Progressive Multifocal / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D008875:Middle Aged; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D016329:Sp1 Transcription Factor; D054322:tat Gene Products, Human Immunodeficiency Virus