Typing of human polyomavirus JC virus on the basis of restriction fragment length polymorphisms

Abstract

JC virus DNA clones from the urine of nonimmunosuppressed Japanese individuals regularly contain an archetypal regulatory sequence which may have generated various regulatory sequences of JC virus isolates from patients with progressive multifocal leukoencephalopathy (PML). In this study, we established 15 new clones from the urine of Dutch, German, and Taiwanese healthy volunteers and patients. Most of these clones contained regulatory sequences essentially identical to the archetypal regulatory sequence. These clones, along with two representative urine-derived clones in Japan and five clones from the brains of PML patients (four established in the United States and one established in Japan), were analyzed with a number of restriction enzymes. We found nine restriction fragment length polymorphisms by which all clones were classified into either of the two types, A and B. Type A contained only clones from the West, while type B contained some from the West and all from eastern Asia. Each type contained both urine-derived and PML-derived clones. Furthermore, there was a close relationship between some urine-derived clones and some PML-derived clones in restriction site mapping analysis. These findings support the adaptation hypothesis which has been postulated to explain the genesis of PML-type JC viruses.