There have been no long-term systematic analyses of the molecular epidemiology of human parvovirus B19 (B19V). We investigated the variations of nucleotide sequences of B19V strains collected in Sapporo, Japan, from 1980 to 2008. In that period, six outbreaks of erythema infectiosum occurred regularly at 5-year intervals. The B19V strains collected successively, regardless of the outbreak, were analyzed for nucleotide variation in the subgenomic NS1-VP1u junction. The isolated strains can be classified into 10 subgroups. Two patterns of change of endemic strains were observed. One was a dynamic replacement of strains that occurred almost every 10 years, and the other was a gradual change consisting of an accumulation of point mutations.Human parvovirus B19 (B19V), a small, nonenveloped, single-stranded DNA virus, belongs to the genus Erythrovirus and the family Parvoviridae and is the only erythrovirus known to be pathogenic in humans. B19V usually transmits via a respiratory route and can also be infectious in blood products or blood components (4). B19V DNA replicates restrictively within erythrocyte precursors in bone marrow (23). The most common presentation of B19V infection is erythema infectiosum (fifth disease), which is generally benign and self-limiting (1). B19V causes aplastic crisis in patients with congenital hemolytic anemia (25). Many reports suggest an association between B19V infection and various clinical manifestations, such as hydrops fetalis, arthritis, hepatitis, and meningoencephalitis (2,5,26,33).The function of NS1, which is composed of 671 amino acids (aa), is related to the transactivation of protein for viral DNA replication, and NS1 is known to have cytotoxic properties (9,18). Another open reading frame encodes both VP1 (781 aa) and VP2 (554 aa) for capsids. VP1 and VP2 are identical except for the additional 227-aa N terminus called the VP1 unique region (VP1u), which is exposed to the surface of infected cells and the target sites of neutralizing antibodies (17,27).Genetic diversity among B19V strains has been considered to be low, and nucleotide variation is less than 1 to 2% for the whole genome (7, 10). However, recent reports suggest that the genetic diversity of B19V is greater than previously believed. B19V strains are now subdivided into three distinct genotypes: 1, 2, and 3 (11,20,21,29). Genotype 1 is thought to be the most common worldwide.Almost all reports about polygenetic analyses of B19V sequences have shown that genetic diversity is correlated with the respective places and years of isolation (7,8,10,13). However, these studies were based on unsystematic data with an uncoordinated distribution of places and years because sampling occurred at random. We have screened serum samples collected over the last 3 decades for B19V DNA using a nested PCR assay and analyzed these sequences to determine the epidemiological distribution and transmission patterns of B19V. Our study tracks the genetic evolution of the virus more precisely because it is based on serum samples col...