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Updated: Aug 18, 2026
Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry
Published on: June 26, 2019
Investigation on the role of cell transcriptional factor Sp1 and HIV-1 TAT protein in PML onset or development
M Mischitelli1, D Fioriti, M Videtta
1Department of Public Health Sciences, University of Rome La Sapienza, Italy.
Abstract:
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.
Insights
Human immunodeficiency virus (HIV) coinfection synergizes with JC virus (JCV) replication in the central nervous system. HIV-positive individuals show NCCR enhancements, suggesting a role in JCV pathogenesis.
Area of Science:
- Neurovirology
- Molecular Virology
- Immunology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by JC virus (JCV).
- PML is strongly associated with immunodepression, particularly in patients with acquired immunodeficiency syndrome (AIDS).
- JCV's non-coding control region (NCCR) regulates viral replication and exhibits significant genetic variability, influencing disease pathogenesis.
Purpose of the Study:
- To investigate the presence and variants of the JCV genome in cerebrospinal fluid (CSF) of HIV-positive and HIV-negative PML patients.
- To analyze specific NCCR elements, including Sp1 binding sites (boxes B and D) and the up-TAR sequence (box C), in relation to HIV status.
- To explore potential synergistic interactions between HIV-1 and JCV in the central nervous system (CNS).
Main Methods:
- Polymerase chain reaction (PCR) was used to detect the JCV genome in CSF samples.
- DNA sequencing was employed to analyze the NCCR structure of JCV variants.
- Specific focus was placed on analyzing Sp1 binding sites and the up-TAR sequence within the NCCR.
Main Results:
- In HIV-positive subjects with PML, all analyzed NCCR structures exhibited enhancements of the up-TAR element.
- In contrast, HIV-negative subjects with PML consistently retained both Sp1 binding sites (boxes B and D).
- These findings suggest distinct NCCR profiles correlating with HIV coinfection status.
Conclusions:
- A synergistic interaction between HIV-1 and JCV in the CNS is supported by the observed NCCR alterations.
- Sp1 binding sites may be crucial for JCV replication in the absence of HIV coinfection.
- The up-TAR element's enhancement in HIV-positive individuals could contribute to increased JCV replication and PML development in this population.
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