Unique region of the minor capsid protein of human parvovirus B19 is exposed on the virion surface.

Rosenfeld, Stephen J.; Yoshimoto, Kohji; Kajigaya, Sachiko; Anderson, Stacie M.; Young, Neal S.; Field, Anne M.; Warrener, Paul; Bansal, Gulshan; Collett, Marc S.

doi:10.1172/jci115812

Cited by 101 publications

(71 citation statements)

References 19 publications

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“…Originally inside the capsid (except for B19) (38), the unique N-VP1 of parvovirus becomes exposed in vivo during the entry process (35,50) or in vitro by heat or urea (4,7,21,50). Although it has not been directly shown to occur within the endosomal compartments, the externalization of N-VP1 from CPV occurs in the cytoplasm as early as 2 h postinfection (46).…”

Section: Discussionmentioning

confidence: 99%

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Low pH-Dependent Endosomal Processing of the Incoming Parvovirus Minute Virus of Mice Virion Leads to Externalization of the VP1 N-Terminal Sequence (N-VP1), N-VP2 Cleavage, and Uncoating of the Full-Length Genome

Mani

Baltzer

Valle

et al. 2006

J Virol

118

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Minute virus of mice (MVM) enters the host cell via receptor-mediated endocytosis. Although endosomal processing is required, its role remains uncertain. In particular, the effect of low endosomal pH on capsid configuration and nuclear delivery of the viral genome is unclear. We have followed the progression and structural transitions of DNA full-virus capsids (FC) and empty capsids (EC) containing the VP1 and VP2 structural proteins and of VP2-only virus-like particles (VLP) during the endosomal trafficking. Three capsid rearrangements were detected in FC: externalization of the VP1 N-terminal sequence (N-VP1), cleavage of the exposed VP2 N-terminal sequence (N-VP2), and uncoating of the full-length genome. All three capsid modifications occurred simultaneously, starting as early as 30 min after internalization, and all of them were blocked by raising the endosomal pH. In particles lacking viral single-stranded DNA (EC and VLP), the N-VP2 was not exposed and thus it was not cleaved. However, the EC did externalize N-VP1 with kinetics similar to those of FC. The bulk of all the incoming particles (FC, EC, and VLP) accumulated in lysosomes without signs of lysosomal membrane destabilization. Inside lysosomes, capsid degradation was not detected, although the uncoated DNA of FC was slowly degraded. Interestingly, at any time postinfection, the amount of structural proteins of the incoming virions accumulating in the nuclear fraction was negligible. These results indicate that during the early endosomal trafficking, the MVM particles are structurally modified by low-pH-dependent mechanisms. Regardless of the structural transitions and protein composition, the majority of the entering viral particles and genomes end in lysosomes, limiting the efficiency of MVM nuclear translocation.

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Section: Discussionmentioning

confidence: 99%

“…With the exception of B19 (38), the unique N-terminal sequence (N-VP1) is internal in the parvovirus capsid and becomes exposed during the entry process (35,46). N-VP1 can also be exposed by heat or urea (4,7,21,50).…”

mentioning

confidence: 99%

Low pH-Dependent Endosomal Processing of the Incoming Parvovirus Minute Virus of Mice Virion Leads to Externalization of the VP1 N-Terminal Sequence (N-VP1), N-VP2 Cleavage, and Uncoating of the Full-Length Genome

Mani

Baltzer

Valle

et al. 2006

J Virol

118

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“…B19 viral particles possess icosahedral symmetry (20 sided), consisting of 60 capsomers that are composed predominantly of VP2 (9). VP2 appears to facilitate viral attachment onto cells via its amino terminal end, which protrudes from the external virion surface (10). NS1 is a multifunctional protein; it has regulatory functions in the viral life cycle, allowing for replication of viral DNA and viral packaging; and it interferes with cellular signaling pathways, leading to apoptosis of host cells (11) and target cell cytotoxicity (12).…”

mentioning

confidence: 99%

Parvovirus B19 and the Kidney

Waldman¹,

Kopp²

2007

Clinical Journal of the American Society of Nephrology

112

105

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“…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).…”

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confidence: 99%

Phylogenetic Evidence for the Rapid Evolution of Human B19 Erythrovirus

Shackelton

Holmes

2006

J Virol

121

114

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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...

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Unique region of the minor capsid protein of human parvovirus B19 is exposed on the virion surface.

Cited by 101 publications

References 19 publications

Low pH-Dependent Endosomal Processing of the Incoming Parvovirus Minute Virus of Mice Virion Leads to Externalization of the VP1 N-Terminal Sequence (N-VP1), N-VP2 Cleavage, and Uncoating of the Full-Length Genome

Low pH-Dependent Endosomal Processing of the Incoming Parvovirus Minute Virus of Mice Virion Leads to Externalization of the VP1 N-Terminal Sequence (N-VP1), N-VP2 Cleavage, and Uncoating of the Full-Length Genome

Parvovirus B19 and the Kidney

Phylogenetic Evidence for the Rapid Evolution of Human B19 Erythrovirus

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