Identification of a nonconventional motif necessary for the nuclear import of the human parvovirus B19 major capsid protein (VP2)

Pillet, Sylvie; Annan, Zeinab; Fichelson, Serge; Morinet, F.

doi:10.1016/s0042-6822(02)00047-8

Cited by 28 publications

(25 citation statements)

References 21 publications

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“…The relative abundance of the two protein species is in part regulated by the relative abundance of the respective mRNAs, in part from efficiency of translation initiation [111], and also may depend on effects linked to the 3 UTR region of specific mRNAs [113]. A nonconsensus basic motif in the C-terminal region of VP1/2 mediates transport of capsid proteins to the nucleus, where capsid assembly and genome packaging may occur [123]. As in the case for NS protein, neither posttranslational modifications nor processing has been documented.…”

Section: Vp Proteinsmentioning

confidence: 99%

Parvovirus B19 Achievements and Challenges

Gallinella

2013

ISRN Virology

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Parvovirus B19 is a widespread human pathogenic virus, member of the Erythrovirus genus in the Parvoviridae family. Infection can be associated with an ample range of pathologies and clinical manifestations, whose characteristics and outcomes depend on the interplay between the pathogenetic potential of the virus, its adaptation to different cellular environments, and the physiological and immune status of the infected individuals. The scope of this review is the advances in knowledge on the biological characteristics of the virus and of virus-host relationships; in particular, the interactions of the virus with different cellular environments in terms of tropism and ability to achieve a productive replicative cycle, or, on the contrary, to establish persistence; the consequences of infection in terms of interference with the cell physiology; the process of recognition of the virus by the innate or adaptive immune system, hence the role of the immune system in controlling the infection or in the development of clinical manifestations. Linked to these issues is the continuous effort to develop better diagnostic algorithms and methods and the need for development of prophylactic and therapeutic options for B19V infections.

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Section: Vp Proteinsmentioning

confidence: 99%

Parvovirus B19 Achievements and Challenges

Gallinella

2013

ISRN Virology

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“…This domain is critical for B19V entry; virions with mutations in the VP1u region are not able to enter into the nucleus of the infected cell (27). No NLS implicated in nuclear entry has been described so far for B19V; a NLS has been localized to the C-terminal region of VP2, but its role in the entry of B19V has not been studied (78).…”

Section: B19v Entry Into Cellsmentioning

confidence: 99%

Advances in Human B19 Erythrovirus Biology

Servant‐Delmas

Lefrère

Morinet³

et al. 2010

J Virol

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Since its discovery, human parvovirus B19 (B19V), now termed erythrovirus, has been associated with many clinical situations (neurological and myocardium infections, persistent B19V DNAemia) in addition to the prototype clinical manifestations, i.e., erythema infectiosum and erythroblastopenia crisis. In 2002, the use of new molecular tools led to the characterization of three different genotypes of human B19 erythrovirus. Although the genomic organization is conserved, the geographic distribution of the different genotypes varies worldwide, and the nucleotidic divergences can impact the molecular diagnosis of B19 virus infection. The cell cycle of the virus remains partially unresolved; however, recent studies have shed light on the mechanism of cell entry and the interactions of B19V proteins with apoptosis pathways.Before the recent descriptions of human bocavirus (2) and human parvovirus 4 (PARV4) (41), parvovirus B19 ([B19V] or erythrovirus B19) was the only known member of the Parvoviridae family to infect humans. The Erythrovirus genus contains B19V, erythroviruses that infect several simian species, and the parvovirus from Manchurian chipmunks (87a). These viruses share the remarkable property of replicating in and destroying erythroid progenitors. This strong in vitro tropism explains the difficulties in studying the replicative cycle of these viruses; indeed, the in vitro production and culture of erythroid progenitor cells remain delicate. An infectious B19V clone was described only recently (102), and its use, although mostly limited and allowing only a small amount of progeny production, led to constructions of recombinant viruses that were helpful in understanding the steps of the virus life cycle and the toxicity of the virus. Discovered in 1975 (19), B19V can cause a wide range of mild and self-limiting clinical manifestations, such as erythema infectiosum (fifth disease) and oligoarthritis (98). B19V infection can also cause acute anemia by aplastic crisis in patients whose red blood cells have shortened survival times (i.e., patients with sickle cell disease, thalassemia, spherocytosis, or any disorder of hemoglobin gene expression or red cell membrane constitution), chronic anemia in patients with congenital immunodeficiencies or human immunodeficiency virus (HIV) infection or who are undergoing chemotherapy for malignancies or organ transplants (48, 58), and hydrops fetalis or intrauterine death in infected fetuses (86). Recently, cases of neurological manifestations have been associated with B19V infection (22), as have myocardium infections (4,5,47,83), and the spectrum of B19V-linked diseases may further increase. CLINICAL MANIFESTATIONSThe primary route of transmission of B19V is the respiratory tract (via aerosol droplets), with a majority of infections occurring during childhood, but the infection may also be transmitted by organ transplantation and especially by transfusion of blood components, in particular by packed red cells from blood collected during the short preseroconversion vi...

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“…1). It was also demonstrated for the B19 human parvovirus that an unconventional NLS (KLGPR KATGRW) containing few basic amino acids was responsible for VP2 protein transport to the nucleus (34). This region is not conserved in PPV (TAKMRSSMNW).…”

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confidence: 99%

Classic Nuclear Localization Signals and a Novel Nuclear Localization Motif Are Required for Nuclear Transport of Porcine Parvovirus Capsid Proteins

Boisvert

Bouchard-Lévesque

Fernandes

et al. 2014

J Virol

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Nuclear targeting of capsid proteins (VPs) is important for genome delivery and precedes assembly in the replication cycle of porcine parvovirus (PPV). Clusters of basic amino acids, corresponding to potential nuclear localization signals (NLS), were found only in the unique region of VP1 (VP1up, for VP1 unique part). Of the five identified basic regions (BR), three were important for nuclear localization of VP1up: BR1 was a classic Pat7 NLS, and the combination of BR4 and BR5 was a classic bipartite NLS. These NLS were essential for viral replication. VP2, the major capsid protein, lacked these NLS and contained no region with more than two basic amino acids in proximity. However, three regions of basic clusters were identified in the folded protein, assembled into a trimeric structure. Mutagenesis experiments showed that only one of these three regions was involved in VP2 transport to the nucleus. This structural NLS, termed the nuclear localization motif (NLM), is located inside the assembled capsid and thus can be used to transport trimers to the nucleus in late steps of infection but not for virions in initial infection steps. The two NLS of VP1up are located in the N-terminal part of the protein, externalized from the capsid during endosomal transit, exposing them for nuclear targeting during early steps of infection. Globally, the determinants of nuclear transport of structural proteins of PPV were different from those of closely related parvoviruses. IMPORTANCEMost DNA viruses use the nucleus for their replication cycle. Thus, structural proteins need to be targeted to this cellular compartment at two distinct steps of the infection: in early steps to deliver viral genomes to the nucleus and in late steps to assemble new viruses. Nuclear targeting of proteins depends on the recognition of a stretch of basic amino acids by cellular transport proteins. This study reports the identification of two classic nuclear localization signals in the minor capsid protein (VP1) of porcine parvovirus. The major protein (VP2) nuclear localization was shown to depend on a complex structural motif. This motif can be used as a strategy by the virus to avoid transport of incorrectly folded proteins and to selectively import assembled trimers into the nucleus. Structural nuclear localization motifs can also be important for nuclear proteins without a classic basic amino acid stretch, including multimeric cellular proteins.

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Identification of a nonconventional motif necessary for the nuclear import of the human parvovirus B19 major capsid protein (VP2)

Cited by 28 publications

References 21 publications

Parvovirus B19 Achievements and Challenges

Parvovirus B19 Achievements and Challenges

Advances in Human B19 Erythrovirus Biology

Classic Nuclear Localization Signals and a Novel Nuclear Localization Motif Are Required for Nuclear Transport of Porcine Parvovirus Capsid Proteins

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