Phylogenetic Evidence for the Rapid Evolution of Human B19 Erythrovirus

Abstract

Human B19 erythrovirus is a ubiquitous viral pathogen, commonly infecting individuals before adulthood. As with all autonomous parvoviruses, its small single-stranded DNA genome is replicated with host cell machinery. While the mechanism of parvovirus genome replication has been studied in detail, the rate at which B19 virus evolves is unknown. By inferring the phylogenetic history and evolutionary dynamics of temporally sampled B19 sequences, we observed a surprisingly high rate of evolutionary change, at approximately 10 ؊4 nucleotide substitutions per site per year. This rate is more typical of RNA viruses and suggests that high mutation rates are characteristic of the Parvoviridae.Human B19 erythrovirus was first discovered in the serum of healthy blood donors (3) and has since been detected worldwide. Infection usually occurs in childhood, through respiratory droplets, and by age 15 approximately 50% of children have antibodies to the virus. Most childhood infections are asymptomatic, with erythema infectiosum, probably caused by the formation of immune complexes, the most frequent complication. In adults, however, infection often results in arthropathy and in some cases causes transient aplastic crisis. In immunocompromised individuals a persistent infection usually occurs, resulting in red cell aplasia, while transplacental transmission can lead to miscarriage or hydrops fetalis (22).Human erythroviruses belong to the family Parvoviridae, whose single-stranded (ss) DNA genomes are among the smallest of all DNA viruses. B19 virus is ϳ5.5 kb in length with two major open reading frames flanked by inverted terminal repeats, part of which form hairpin stems for priming replication through a double-stranded (ds) intermediate (2). The first open reading frame encodes the nonstructural (NS1) protein, while the second encodes the capsid proteins VP1 and VP2, which are in frame and colinear with the exception of an additional 227 amino acids at the N terminus of VP1. Amino acid variability is high in the VP1 unique region (19), which is surface exposed and the target site of neutralizing antibodies (8, 13).Unlike large dsDNA viruses, all autonomous parvoviruses replicate with host cell machinery (10). A common assumption in studies of viral evolution is that DNA viruses have low rates of evolutionary change, near those of their hosts, as observed in the large dsDNA herpesviruses (7, 14) and the small dsDNA human papillomaviruses (1). However, it was recently observed that one group of small ssDNA viruses, the carnivore parvoviruses, have a rate of nucleotide substitution many orders of magnitude higher, at approximately 1 ϫ 10 Ϫ4 substitutions/site/year, that is within the range seen in RNA viruses (17). It is currently unclear whether this unexpectedly high rate is characteristic of the carnivore parvoviruses alone or whether it typifies the entire Parvoviridae family. To address this issue we estimated the rate of nucleotide substitution in the human virus B19, a distant relative of the carnivore parvoviruses. B...

Simultaneous persistence of multiple genome variants of human parvovirus B19

“…Especially during the initial phase of B19V infection, characterized by high levels of viral replication, there might be a greater chance of appearance of inaccurately replicated B19V DNA; although, the viral DNA is replicated by the host cell machinery. It has been recently speculated by others (Ló pez-Bueno et al, 2003;Shackelton & Holmes, 2006) that the fidelity and the proofreading activity of the enzymic complex containing the host DNA polymerase, recruited cellular replication factors and the viral NS1 protein may not be as efficient in single-stranded DNA viruses as expected so far. Furthermore, it has been demonstrated that B19V, similar to parvoviruses infecting animals, has a high rate of evolutionary changes that is more typical of RNA viruses (Ló pez- Bueno et al, 2006;Shackelton et al, 2005;Shackelton & Holmes, 2006).…”

“…It has been recently speculated by others (Ló pez-Bueno et al, 2003;Shackelton & Holmes, 2006) that the fidelity and the proofreading activity of the enzymic complex containing the host DNA polymerase, recruited cellular replication factors and the viral NS1 protein may not be as efficient in single-stranded DNA viruses as expected so far. Furthermore, it has been demonstrated that B19V, similar to parvoviruses infecting animals, has a high rate of evolutionary changes that is more typical of RNA viruses (Ló pez- Bueno et al, 2006;Shackelton et al, 2005;Shackelton & Holmes, 2006). Since the NS1 gene evolves at a similar rate as the gene for VP2, it was suggested that immune selection is not the primary cause of the high substitution rate in B19V.…”

“…Presuming that infections were acquired sequentially, one might speculate that the incoming infection might exert an effect on the viral genome already resident. Alternatively, given the recently described genetic instability of the virus (Shackelton & Holmes, 2006) and the fact that genotype 2 virus has widely disappeared from circulation but its genome can be frequently detected in tissue from people born before~1960 (Norja et al, 2006), possibly a more attractive speculation is that the 'new' genotype 1 virus has evolved from the genotype 2 virus under immune pressure raised by infections with genotype 2 virus. In this context, it is noteworthy to mention that in earlier studies in the Aleutian mink disease parvovirus system more than one viral genome sequence was observed in highly virulent isolates (Gottschalck et al, 1991).…”

High-Frequency Reversion of Geminivirus Replication Protein Mutants during Infection

“…In contrast, high mutation rates (ca. 10 Ϫ4 ) have been reported for parvoviruses (35,64,65) and circoviruses (6,21). Like geminiviruses, these viruses have ssDNA genomes that replicate via rolling-circle mechanisms.…”

Evolution of Chloroplast 16S Ribosome RNA Dependent Spectinomycin Resistance and Implications for Chloroplast Transformation

“…In order to prove that mutation happened on high concentration of spectinomycin, the 16S rDNA of a green shoot which resists 500 mg l -1 spectinomycin was sequenced, resulting in a novel mutation site was found as shown in Figure 3. It is widely accepted on human diseases study that there is a strong correlation between selective pressure and the nucleotide substitution rate for distinct virus genes (Shackelton & Holmes, 2006;Shackelton et al, 2005). For example, capsid proteins of porcine parvovirus (PPV) interact with the host immune system.…”