The use of more intensive antiretroviral therapies, such as HAART, in the treatment of HIV infection has led to a marked reduction in morbidity and mortality associated with AIDS. This happens because the incidence of the major opportunistic infections and of many AIDS-related neurological disorders dramatically decreased, but the Progressive Multifocal Leukoencephalopathy (PML) is still observed with a prevalence up to 5% in AIDS patients. Although the advent of HAART did not affect so much the incidence of PML, some changes in the clinical course of this fatal disease have been observed. In fact PML usually results in death within 3-6 months of diagnosis (PML fast progressing patients), but to date there are reports of remission of PML during HAART and several PML cases have prolonged rate of survival, up to one year from the onset of the disease (PML slow progressing patients). In this project we are hypothesizing that either a particular JCV genotype or a specific TCR rearrangement or both could affect the disease progress, slowing down the process of demyelination. Moreover several cases suffering with a PML-like Leukoencephalopathy, called non- determined Leukoencephalopathy (NDLE) with no evidence of JCV genome in CSF have been lately reported. Our suggestion is that the result of an improved immune status upon HAART could also lead to an imbalanced expression of cytokines and immunomodulators by peripheral lymphocytes that may affect. In order to verify our hypothesis and better understand the etiology, the development and the progress of the new variant of PML and of the novel JCV negative-leukoencephalopathy, we are proposing to enroll in a longitudinal study, patients affected with fast and slow progressing PML, patients with suspected NDLE, HIV+ patients without any neurological disorders and healthy controls, whose biological samples will be collected at different times of the diseases and subjected to immunological, virological, genetic conventional and innovative examinations as described in the proposal. ? ?

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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NeuroAIDS and other End-Organ Diseases Study Section (NAED)
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Joseph, Jeymohan
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Saint Joseph Hospital
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Delbue, Serena; Elia, Francesca; Carloni, Camilla et al. (2012) JC virus load in cerebrospinal fluid and transcriptional control region rearrangements may predict the clinical course of progressive multifocal leukoencephalopathy. J Cell Physiol 227:3511-7
Delbue, Serena; Comar, Manola; Ferrante, Pasquale (2012) Review on the relationship between human polyomaviruses-associated tumors and host immune system. Clin Dev Immunol 2012:542092
Zanin, Valentina; Delbue, Serena; Marcuzzi, Annalisa et al. (2012) Specific protein profile in cerebrospinal fluid from HIV-1-positive cART-treated patients affected by neurological disorders. J Neurovirol 18:416-22
Delbue, Serena; Ferraresso, Mariano; Elia, Francesca et al. (2012) Investigation of polyomaviruses replication in pediatric patients with nephropathy receiving rituximab. J Med Virol 84:1464-70
Tremolada, Sara; Delbue, Serena; Castagnoli, Lorenzo et al. (2010) Mutations in the external loops of BK virus VP1 and urine viral load in renal transplant recipients. J Cell Physiol 222:195-9
Tremolada, Sara; Delbue, Serena; Larocca, Sara et al. (2010) Polymorphisms of the BK virus subtypes and their influence on viral in vitro growth efficiency. Virus Res 149:190-6
Mancuso, Roberta; Hernis, Ambra; Cavarretta, Rosella et al. (2010) Detection of viral DNA sequences in the cerebrospinal fluid of patients with multiple sclerosis. J Med Virol 82:1051-7
Delbue, Serena; Tremolada, Sara; Elia, Francesca et al. (2010) Lymphotropic polyomavirus is detected in peripheral blood from immunocompromised and healthy subjects. J Clin Virol 47:156-60
Visco, Carlo; Marchioni, Enrico; Pomponi, Fabrizio et al. (2009) Progressive multifocal leuconcephalopathy and autoimmune haemolytic anemia in chronic lymphocytic leukaemia: more than a fortuitous combination? Ann Hematol 88:189-91
Delbue, Serena; Branchetti, Emanuela; Bertolacci, Simone et al. (2009) JC virus VP1 loop-specific polymorphisms are associated with favorable prognosis for progressive multifocal leukoencephalopathy. J Neurovirol 15:51-6

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