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Pathogenesis and Immunity

JC Virus Regulatory Region Tandem Repeats in Plasma and Central Nervous System Isolates Correlate with Poor Clinical Outcome in Patients with Progressive Multifocal Leukoencephalopathy

Luz-Andrea Pfister, Norman L. Letvin, Igor J. Koralnik
Luz-Andrea Pfister
Division of Viral Pathogenesis, Department of Medicine, and
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Norman L. Letvin
Division of Viral Pathogenesis, Department of Medicine, and
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Igor J. Koralnik
Division of Viral Pathogenesis, Department of Medicine, and
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215
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DOI: 10.1128/JVI.75.12.5672-5676.2001
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    Fig. 1.

    Sequencing results of the JCV RR. On the top is a representation of the MAD-1 and archetype JCV RR. The nucleotide numbers are based on the prototype MAD-1 sequence. The known transcription regulation factor binding sites are indicated and include the lytic control element (Lytic E), nuclear factor 1 (NF-1), and c-Jun. Each 98-bp unit is represented by an open box. The TATA box is represented by TATA. The archetype contains only one 98-bp unit with two inserts. Black box, 23-bp insert; checkered box, 66 bp-insert; dotted lines, deletions in the 98-bp units or in the 23- or 66-bp inserts; grey box, region downstream of the 98-bp units. Some clones contain fragments of this region inserted in the second 98-bp unit. MAD-1 contains an adenine at positions 85 and 183, compared with all other sequences that contain guanine at these positions. Asterisks, single mutations; scissors, single nucleotide deletions in the TATA box. (A) Sequencing results of HIV+ PML progressor patients 1 to 8. At the right of each sequence is the number of clones obtained per anatomic compartment. The first sequence of patient no. 1 has a large deletion in the second 98-bp unit that is replaced by a fragment identical to nucleotides 208 to 247 (striped box) containing an NF-1 predicted binding site and next to it a c-Jun binding site. Patient 3, 4, and 6 sequences have smaller fragments of the region nt 208 to 250 inserted in the second 98-bp unit; only the patient 3 sequence contains the full length of the NF-1 binding site. (B) HIV-negative PML progressors. (C) PML survivors. No. 11 is HIV+ and no. 12 is HIV−. (D) HIV+ patients with low CD4+ T-cell counts and other, non-PML neurologic disorders.

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    Types of JCV RRa found in plasma and CNS (brain and CSF) of groups with different clinical outcomes

    Clinical outcome and/or patient characteristicPlasmaCNS
    No. of patientsNo. of clonesNo. (%) of indicated RR typeaNo. of patientsNo. of clonesNo. (%) of indicated RR typea
    AALTRAALTR
    PML progressor, HIV+/HIV− 543020 (46)23 (54)9881 (1)12 (14)75 (85)
    PML survivor, HIV+/HIV− 2129 (75)03 (25)11010 (100)00
    HIV+/OND4248 (33)14 (58)2 (8)
    Total11791098
    • ↵a A, archetype; AL, archetype like; TR, tandem repeats.

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JC Virus Regulatory Region Tandem Repeats in Plasma and Central Nervous System Isolates Correlate with Poor Clinical Outcome in Patients with Progressive Multifocal Leukoencephalopathy
Luz-Andrea Pfister, Norman L. Letvin, Igor J. Koralnik
Journal of Virology Jun 2001, 75 (12) 5672-5676; DOI: 10.1128/JVI.75.12.5672-5676.2001

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JC Virus Regulatory Region Tandem Repeats in Plasma and Central Nervous System Isolates Correlate with Poor Clinical Outcome in Patients with Progressive Multifocal Leukoencephalopathy
Luz-Andrea Pfister, Norman L. Letvin, Igor J. Koralnik
Journal of Virology Jun 2001, 75 (12) 5672-5676; DOI: 10.1128/JVI.75.12.5672-5676.2001
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KEYWORDS

JC virus
Leukoencephalopathy, Progressive Multifocal
Regulatory Sequences, Nucleic Acid
Tandem Repeat Sequences

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