Typing of urinary JC virus DNA offers a novel means of tracing human migrations

Abstract

Although polyomavirus JC (JCV) is the proven pathogen of progressive multifocal leukoencephalopathy, the fatal demyelinating disease, this virus is ubiquitous as a usually harmless symbiote among human beings. JCV propagates in the adult kidney and excretes its progeny in urine, from which JCV DNA can readily be recovered. The main mode of transmission of JCV is from parents to children through long cohabitation. In this study, we collected a substantial number of urine samples from native inhabitants of 34 countries in Europe, Africa, and Asia. A 610-bp segment of JCV DNA was amplified from each urine sample, and its DNA sequence was determined. A worldwide phylogenetic tree subsequently constructed revealed the presence of nine subtypes including minor ones. Five subtypes (EU, Af2, B1, SC, and CY) occupied rather large territories that overlapped with each other at their boundaries. The entire Europe, northern Africa, and western Asia were the domain of EU, whereas the domain of Af2 included nearly all of Africa and southwestern Asia all the way to the northeastern edge of India. Partially overlapping domains in Asia were occupied by subtypes B1, SC, and CY. Of particular interest was the recovery of JCV subtypes in a pocket or pockets that were separated by great geographic distances from the main domains of those subtypes. Certain of these pockets can readily be explained by recent migrations of human populations carrying these subtypes. Overall, it appears that JCV genotyping promises to reveal previously unknown human migration routes: ancient as well as recent.

Molecular Epidemiology of Human Polyomavirus JC in the Biaka Pygmies and Bantu of Central Africa

“…Based on sequence analysis of JCV complete genomes, as well as segments of the VP1 and T antigen genes, JCV can be classified into several geographically based genotypes and subtypes (Ault & Stoner 1992, Agostini et al 1995, 1997d, Sugimoto et al 1997. The major genotypes so far described are Type 1, which is of European origin, Type 2, which is Asian, and Types 3 and 6 which are African in origin (Agostini et al 1995(Agostini et al , 1998.…”

“…This is followed by persistent infection of the kidneys from which JCV is excreted in urine. Studies with polymerase chain reaction (PCR) show that 30-70% of adults worldwide are positive for JC viruria (Agostini et al 1996, Sugimoto et al 1997, Shah et al 1998. JCV has been established as the causative agent in progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system (Zurhein & Chou 1965).…”

Dispersal of southeastern Asians based on a global phylogenetic analysis of JC polyomavirus isolates of genotype SC

“…In the current study, we focused our attention on an Asian genotype of JCPyV named SC. Sugimoto et al (1997) found that this genotype occurs mainly in southeastern Asia and southern China, with minor SC isolates in central and northern Asia and southern Africa. Using phylogenetic analysis based on complete viral DNA sequences, Saruwatari et al (2002b) subclassified many SC isolates in Myanmar, together with a few in other countries, into six subgroups, SC-a to -f. Most subgroups (SC-a to -e) contained isolates in Myanmar, but one (SC-f) included isolates in various regions of southeastern Asia and southern China.…”

“…southern Africa and southern Japan) remote from the areas where SC is most common (i.e. Southeast Asia), although these were detected at only a low frequency (Sugimoto et al, 1997;Kitamura et al, 1998); (6) most SC isolates in Guam probably belonged to the SC-f subgroup, as these had the unique pentanucleotide deletion in the regulatory region (see above). In addition, a single isolate in Hawaii was grouped in the non-SC-f category based on the SNP analysis, consistent with the phylogenetic analysis of the complete viral DNA sequences described above.…”

“…In most adults, renal JCPyV is not latent but replicates to excrete progeny into urine (Kitamura et al, , 1994Agostini et al, 1996). JCPyV strains around the world can be classified into more than ten major genotypes, with each genotype occupying a unique geographical domain (Sugimoto et al, 1997;Cui et al, 2004;Yogo et al, 2004). Hence, JCPyV genotyping analysis has provided new insights into the origins of various ethnic groups throughout the world .…”