Multiple JC Virus Genomes from One Patient

Abstract

SUMMARY JC virus was previously isolated from the urine and from diseased brain of a patient with progressive multifocal leukoencephalopathy. The DNAs of these isolates, MAD-7 and MAD-8 respectively, were shown in this study to be mixtures of several different full-length genomes. By differences in their restriction endonuclease cleavage patterns, the genomes were categorized into two types. Type I DNA was defined as that typified by the prototype virus, MAD-l; Type II, that typified by viral DNA molecularly cloned from brain tissue of the MAD-7/8 patient (BrC-8 DNA). MAD-7 DNA was an approximately equal mixture of Type I and Type II; MAD-8 DNA appeared to be homogeneously Type II. These DNAs were molecularly cloned for further studies. Of 17 clones of recombinant MAD-7 (rMAD-7) DNA, nine were Type I and were identical to each other and to MAD-1 DNA. The other eight clones comprised five different species of Type II, none of which was identical to MAD-8 or to BrC-8 DNA. Among 17 recombinant MAD-8 (rMAD-8) clones there were two which contained Type I DNA, which had not been detected in the original viral DNA. The remaining rMAD-8 clones were of Type II. The differences among all these DNAs were primarily in the 'extra' PvulI sites and in the insertions and deletions in the hypervariable regulatory region of the genome (0-67 to 0.72 map unit). Possible explanations for multiple genomes in separate isolates from the same patient are discussed. It is concluded that the observed variation originated in vivo and not during isolation in vitro.

Two Major Types of JC Virus Defined in Progressive Multifocal Leukoencephalopathy Brain by Early and Late Coding Region DNA Sequences

“…Since we find these sites to be in full agreement with type-determining sites in the V-T intergenic region, it is clear that the RFLP-based Types A and B of Yogo et al (1991) correspond to our Types 1 and 2, respectively. However, typing which is not based on known sequence variation tends to be ambiguous, making it difficult to include additional isolates (Grinnell et al, 1983b;Martin & Foster, 1984;Yogo et al, 1991;Takahashi et al, 1992;Tominaga et al, 1992). Using our simple system of type-determining sites, new sequences can be easily classified relative to known strains.…”

“…Classification schemes based on the structure of the regulatory region have been described (Martin et al, 1985;Walker & Frisque, 1986), but it is not clear whether the patterns of sequence rearrangement reflect the genotype of the virus or result from host cell biology. Similarly, typing by restriction fragment length polymorphism (RFLP) (Yogo et al, 1990;Grinnell et al, 1983a, b;Martin & Foster, 1984) has not revealed the kind of clear-cut taxonomy which could lead to simple and unambiguous typing. In general, RFLP typing is a low resolution analysis which misses many informative sequence changes, and leaves doubt as to the actual sequence variations at the sites altered.…”

Different genotypes of human polyomaviruses found in patients with autoimmune diseases in Taiwan

“…It has been speculated that JCV may persist in the kidney in a form termed archetype Bog0 et al, 19901. During the long term immunosuppressive condition, the virus may be reactivated and may rearrange its promoter-enhancer regulatory region by deletion and/or duplications to form different strains and cause PML in brain [Chuke et al, 1986;Dorries, 1984;Frisque et al, 1984;Martin and Foster, 1984;White et al, 19921. This speculation could be correlated with the fact that about 5% of AIDS patients succumb to PML [Berger et al, 1987;Krupp et al, 1985;Kure et al, 1991;Snider et al, 19831. Patients with various autoimmune diseases, such as systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), rheumatoid arthritis (RA), or dermatomyositis/polymyositis (DMIPM), primarily become immunocompromised because of intrinsic abnormalities of the immune system, or immunosuppressive therapy.…”

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

“…3C), is more typical of NCCR variants found in PML patients than Mad-1. This variant contains a repeat structure similar to that of the prototype, with one large deletion and one insertion, as well as several smaller insertions and base changes (316,317). Examples of rearranged NCCRs can be found in many studies that have sequenced, annotated, and aligned multiple NCCRs from PML patients (413,485,552,557).…”