title: The JCPYV DNA load inversely correlates with the viral microrna expression in blood and cerebrospinal fluid of patients at risk of PML.
abstract: BACKGROUND
  In light of their regulatory role, changes in the expression of Polyomavirus JC (JCPyV) microRNAs may be relevant for virus reactivation and the development of progressive multifocal leukoencephalopathy (PML).
  
  
  OBJECTIVE
  To investigate the presence of JCPyV-DNA and JCPyV microRNA expression in clinical specimens of patients at risk for PML.
  
  
  METHODS
  The JCPyV-DNA and microRNA status was assessed in peripheral blood mononuclear cells (PBMCs) and plasma from 100 HIV patients, in serum and cerebrospinal fluid (CSF) from 14 HIV PML patients and in PBMCs and plasma from 50 healthy controls using Multiplex real-time PCR and JCPyV miRNA-J1-3p and -5p stem-loop RT-PCR. The JCPyV-DNA microRNA-expressing region was also sequenced.
  
  
  RESULTS
  A positive JCPyV-DNA status was more prevalent in HIV patients (67%, 67/100) compared to healthy controls (18%, 9/50). Among these, 46% and 42% of the HIV patients and 18% and 0% of the healthy controls were positive based on PBMC and plasma determinations, respectively. PBMC JCPyV microRNA positivity was observed in 22 out of 46 (48%) JCPyV+ HIV patients and in 3 out of 9 (33%) JCPyV+ healthy controls. Moreover, JCPyV microRNAs in exosomes were found in 6 out of 100 (6%) HIV plasma samples, in 12 out of 50 (24%) healthy samples, in 6 out of 14 (43%) serum samples, and in 3 out of 5 (60%) HIV PML CSF samples. Of note, the JCPyV-DNA load was inversely correlated with expression of the viral microRNA. The JCPyV microRNA genomic expression region showed a different combination of three mutations.
  
  
  CONCLUSIONS
  The low levels of JCPyV microRNA expression in HIV patients with high JCPyV-DNA prevalence observed in this study highlight the potential clinical relevance of JCPyV microRNAs in PML risk assessment.
authors: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors: Arianna
authors: A
authors: Rocca
authors: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors: Francesco
authors: F
authors: Martelli
authors: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy.
authors: Serena
authors: S
authors: Delbue
authors: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy.
authors: Pasquale
authors: P
authors: Ferrante
authors: Infectious disease unit, Careggi University Hospital, University of Florence, Florence, Italy.
authors: Dario
authors: D
authors: Bartolozzi
authors: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors: Alberta
authors: A
authors: Azzi
authors: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. Electronic address: simone.giannecchini@unifi.it.
authors: Simone
authors: S
authors: Giannecchini
mesh_terms: D001483:Base Sequence; D060085:Coinfection; D004279:DNA, Viral; D005260:Female; D015870:Gene Expression; D016679:Genome, Viral; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology; D006801:Humans; D007577:JC Virus / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000821:virology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000453:epidemiology / Q000821:virology*; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D035683:MicroRNAs; D012367:RNA, Viral
keywords: Exosomes; HIV; JCPyV; MicroRNA expression; PML