Asian genotypes of JC virus in Native Americans and in a Pacific Island population: markers of viral evolution and human migration

Abstract

The human polyomavirus JC (JCV) causes the central nervous system demyelinating disease progressive multifocal leukoencephalopathy. Previously, we showed that 40% of Caucasians in the United States excrete JCV in the urine as detected by PCR. We have now studied 68 Navaho from New Mexico, 25 Flathead from Montana, and 29 Chamorro from Guam. By using PCR amplification of a fragment of the VP1 gene, JCV DNA was detected in the urine of 45 (66%) Navaho, 14 (56%) Flathead, and 20 (69%) Chamorro. Genotyping of viral DNAs in these cohorts by cycle sequencing showed predominantly type 2 (Asian), rather than type 1 (European). Type 1 is the major type in the United States and Hungary. Type 2 can be further subdivided into 2A, 2B, and 2C. Type 2A is found in China and Japan. Type 2B is a subtype related to the East Asian type, and is now found in Europe and the United States. The large majority (56-89%) of strains excreted by Native Americans and Pacific Islanders were the type 2A subtype, consistent with the origin of these strains in Asia. These findings indicate that JCV infection of Native Americans predates contact with Europeans, and likely predates migration of Amerind ancestors across the Bering land bridge around 12,000-30,000 years ago. If JCV had already differentiated into stable modern genotypes and subtypes prior to first settlement, the origin of JCV in humans may date from 50,000 to 100,000 years ago or more. We conclude that JCV may have coevolved with the human species, and that it provides a convenient marker for human migrations in both prehistoric and modern times.

Figure 1

Sequence of Native American and Chamorro JCV type 2A compared with previously defined types and subtypes in the VP1 typing fragment. These sites are in the 215-bp fragment amplified by primers JTP-15 and JTP-16. types 1 and 2 are distinguished at sites 1771, 1818, and 1870 (bold). Subtyping sites are located at positions 1843 and 1850 (type 1), or at 1837 and 1850 (type 2) (italic). type 2C is defined by “T” and “G” at these subtyping sites, but may not be an independent group. The large majority of Navaho (41/46), Flathead (9/16), and Chamorro (17/20) strains are type 2A. All 17 Chamorro type 2A strains have a variant “T” at position no. 1805. The invariant positions listed here define types 3, 4, and 6 (not shown). H = A, T, or C; Y = C or T.

Figure 2

Percent difference between the complete genomic coding region (4,854 bp) of JCV strains. (A) Differences between three Navaho type 2 strains and the prototypes type 1 (Mad-1) and types 2A (Tokyo-1) and 2B (GS/B). Navaho strains #L-254 and #L-264 were classified as type 2A in the short typing fragment, whereas #L-270 was a type 2C. #L-270 falls into the type 2A group based on its closer relationship to type 2A prototype Tokyo-1 (0.45% difference), than to prototype type 2B strain (1.09% difference). Specimen #L-254 was obtained from a 26-year-old female, #L-264 from a 78-year-old female, and #L-270 from a 63-year-old male. Comparison of the coding region sequences used the gap program. (B) Differences between prototype strains of JCV.