Characterization of JC virus in cerebrospinal fluid from HIV-1 infected patients with progressive multifocal leukoencephalopathy: insights into viral pathogenesis and disease prognosis

被引:20
作者
Marzocchetti, Angela
Sanguinetti, Maurizio
Di Giambenedetto, Simona
Cingolani, Antonella
Fadda, Giovanni
Cauda, Roberto
De Luca, Andrea
机构
[1] Univ Cattolica Sacro Cuore, Inst Clin Infect Dis, I-00168 Rome, Italy
[2] Univ Cattolica Sacro Cuore, Inst Microbiol, I-00168 Rome, Italy
关键词
JC Virus; progressive multifocal leukoencephalopathy; cerebrospinal fluid;
D O I
10.1080/13550280701381324
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Objectives. To analyze virological and immunological features of AIDS-related progressive multifocal leukoencepalophathy (PML) and their association to disease prognosis. Methods. In HIV-infected patients with virologically confirmed PML, JC virus (JCV) DNA load and levels of Macrophage Chemoattractant Protein (MCP)-1 were determined in cerebrospinal fluid. JCV genotypes, rearrangements and JCV DNA binding sites for cellular transcription factors were analyzed by sequencing the viral VP1 region and regulatory region (RR). Results. 45 patients were analyzed: 60% were exposed to highly active antiretroviral therapy (HAART) after PML and 24% before the disease onset. JCV DNA load in cerebrospinal fluid was a strong predictor of patients survival. Lower levels of JCV DNA in cerebrospinal fluid were associated with the following virologic factors: viral genotype 4 (p = 0.043), more rearrangements in the RR (p = 0.046), duplication of RR block B (p = 0.028), and duplication of binding sites for cellular transcription factor NF-1 (p = 0.060). In patients with prior antiretroviral exposure there was a trend towards a higher number of binding sites for cellular transcription factors (p = 0.068). Lower JCV load was also predicted by exposure to HAART (p = 0.010), higher baseline CD4 counts (p = 0.009) and higher cerebrospinal fluid MCP-1 levels (p = 0.036). In a multiple regression model, MCP-1 levels were independently associated with JCV load. Conclusion. HAART leads to a partial immune-mediated control of JCV replication; the virus may tend to escape through the selection of rearrangements in the RR, some associated with enhanced viral replication efficiency, other resulting in multiplication of binding sites for cellular transcription factors.
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页码:338 / 346
页数:9
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