Background/ Objectives: Due to the HAART use, the prognosis of Progressive Multifocal Leukoencephalopathy (PML) has changed and has become variable, and thus reliable and easy-to-use markers of PML clinical evolution are needed. The purpose of our study was to determine whether or not specific amino acid substitutions in the genomic region encoding Viral Protein 1 (VP1) outer loops, Transcriptional Control Region (TCR) rearrangements and viral load of JC Virus (JCV), isolated from Cerebrospinal Fluid (CSF) of patients with different forms of PML, could be associated with the progression of the disease. Methods: In the CSF collected from 20, both HIV+ and HIV-, PML patients (9 Fast Progressors-FP- and 11 Slow Progressors-SP), JCV viral load was evaluated by means of specific RealTime PCR. In addition, JCV TCR was isolated in CSF collected from 15 patients, and sequenced by direct nucleotide sequencing, while JCV VP1 outer loops were amplified in CSF collected from 7 patients, cloned, sequenced and analysed using the ExPASy software. Results: JCV viral load was significantly higher (p<0.001) in CSF of FP PML patients (5.51 log copies/ml) than in CSF of SP PML patients (4.14 log copies/ml). All the JCV strains isolated from CSF of SP PML patients showed specific amino acid mutations at four defined hot spots in the VP1 genomic region encoding the outer loops. No significant association was identified between TCR rearrangements and PML clinical evolution. Conclusions: Taken together, the results confirm that high CSF JCV viral load is predictive of poor outcome of PML patients, whereas some specific polymorphisms of VP1 loops are associated with longer survival of patients. Among slow progressors, mutation at Arg-75, recently suggested to be involved in cell recognition and resulting in non-viable virus, is highly frequent. Thus we could hypothesize that the alteration at the defined hot spots determines a decrease in the viral activity and a slow progression of the disease

Identification of markers of Progressive Multifocal Leukoencephalopathy clinical evolution: molecular characterization of JC Virus genome isolated in Cerebrospinal Fluid of HIV+ and HIV- PML patients / S. Delbue, E. Branchetti, R. Maserati, E. Marchioni, E. Tavazzi, P. Ferrante. ((Intervento presentato al convegno HIV infection and the CNS: developed and resource-limited settings tenutosi a san servolo nel 2007.

Identification of markers of Progressive Multifocal Leukoencephalopathy clinical evolution: molecular characterization of JC Virus genome isolated in Cerebrospinal Fluid of HIV+ and HIV- PML patients

S. Delbue
Primo
;
2007

Abstract

Background/ Objectives: Due to the HAART use, the prognosis of Progressive Multifocal Leukoencephalopathy (PML) has changed and has become variable, and thus reliable and easy-to-use markers of PML clinical evolution are needed. The purpose of our study was to determine whether or not specific amino acid substitutions in the genomic region encoding Viral Protein 1 (VP1) outer loops, Transcriptional Control Region (TCR) rearrangements and viral load of JC Virus (JCV), isolated from Cerebrospinal Fluid (CSF) of patients with different forms of PML, could be associated with the progression of the disease. Methods: In the CSF collected from 20, both HIV+ and HIV-, PML patients (9 Fast Progressors-FP- and 11 Slow Progressors-SP), JCV viral load was evaluated by means of specific RealTime PCR. In addition, JCV TCR was isolated in CSF collected from 15 patients, and sequenced by direct nucleotide sequencing, while JCV VP1 outer loops were amplified in CSF collected from 7 patients, cloned, sequenced and analysed using the ExPASy software. Results: JCV viral load was significantly higher (p<0.001) in CSF of FP PML patients (5.51 log copies/ml) than in CSF of SP PML patients (4.14 log copies/ml). All the JCV strains isolated from CSF of SP PML patients showed specific amino acid mutations at four defined hot spots in the VP1 genomic region encoding the outer loops. No significant association was identified between TCR rearrangements and PML clinical evolution. Conclusions: Taken together, the results confirm that high CSF JCV viral load is predictive of poor outcome of PML patients, whereas some specific polymorphisms of VP1 loops are associated with longer survival of patients. Among slow progressors, mutation at Arg-75, recently suggested to be involved in cell recognition and resulting in non-viable virus, is highly frequent. Thus we could hypothesize that the alteration at the defined hot spots determines a decrease in the viral activity and a slow progression of the disease
2007
Settore MED/07 - Microbiologia e Microbiologia Clinica
Identification of markers of Progressive Multifocal Leukoencephalopathy clinical evolution: molecular characterization of JC Virus genome isolated in Cerebrospinal Fluid of HIV+ and HIV- PML patients / S. Delbue, E. Branchetti, R. Maserati, E. Marchioni, E. Tavazzi, P. Ferrante. ((Intervento presentato al convegno HIV infection and the CNS: developed and resource-limited settings tenutosi a san servolo nel 2007.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/211461
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