scholarly journals Human Parvovirus B19 VP2 Empty Capsids Bind to Human Villous Trophoblast Cellsin vitroVia the Globoside Receptor

2004 ◽  
Vol 12 (2) ◽  
pp. 69-78 ◽  
Author(s):  
Carole C. Wegner ◽  
Jeanne A. Jordan
Keyword(s):  
Parvovirus B19 ◽  
Target Cells ◽  
Human Parvovirus B19 ◽  
Trophoblast Cells ◽  
Igm Antibody ◽  
Viral Binding ◽  
Successful Infection ◽  
Villous Trophoblast ◽  
Empty Capsid

Background:Pregnant women acutely infected with human parvovirus B19 (B19) may transmit the virus to the developing fetus. The mechanism whereby the virus interacts with the placenta is unknown. It is known that globoside receptor is required for successful infection of the target cells, which are the highly undifferentiated, actively dividing colony and burst-form units of the erythroid series. Globoside is present on trophoblast cells which have intimate contact with maternal blood, and may therefore serve as a potential route for B19 transmission into the fetal compartment.Objectives:The purpose of this study was to determine whether B19 VP2 capsids could bind to villous trophoblast cells in vitro and whether globoside was involved.Methods:Binding of B19 VP2 empty capsid to first-trimester villous trophoblast cells was assessed by multiple approaches, including ICC using either biotinylated B19 VP2 empty capsid or unlabeled B19 VP2 empty capsid. Quantification of viral binding involvedI125-labeled B19 VP2 empty capsid. Competition studies included excess unlabeled empty capsids or pretreatment with globoside-specific IgM antibody.Results:Linear binding of B19 VP2 capsid to purified villous trophoblast cells in vitro was clearly demonstrated (R2= 0.9524). Competition studies revealed specificity ofI125-labeled B19 VP2 capsid binding to villous trophoblast cells when pretreatment with either 60-fold excess unlabeled B19 capsid or globoside-specific IgM antibody took place. The results illustrated B19's ability to bind in a specific manner to globoside-containing villous trophoblast cells.Conclusion:We speculate that the globoside present on trophoblast cells may play a role in viral binding in vivo, which may facilitate B19 transmission across the maternal–fetal interface.

Impaired genome encapsidation restricts the in vitro propagation of human parvovirus B19

2013 ◽  
Vol 193 (1) ◽  
pp. 215-225 ◽  
Author(s):  
Raphael Wolfisberg ◽  
Nico Ruprecht ◽  
Christoph Kempf ◽  
Carlos Ros
Keyword(s):  
In Vitro Propagation ◽  
Parvovirus B19 ◽  
Human Parvovirus B19 ◽  
Genome Encapsidation

scholarly journals Evidence of Human Parvovirus B19 Infection in the Post-Mortem Brain Tissue of the Elderly

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 582 ◽  
Author(s):  
Sandra Skuja ◽  
Anda Vilmane ◽  
Simons Svirskis ◽  
Valerija Groma ◽  
Modra Murovska
Keyword(s):  
White Matter ◽  
Frontal Lobe ◽  
Brain Tissue ◽  
Morphological Changes ◽  
Structural Characteristics ◽  
Parvovirus B19 ◽  
Elderly Subjects ◽  
Target Cells ◽  
Human Parvovirus B19 ◽  
Pathogenic Potential

After primary exposure, the human parvovirus B19 (B19V) genome may remain in the central nervous system (CNS), establishing a lifelong latency. The structural characteristics and functions of the infected cells are essential for the virus to complete its life cycle. Although B19V has been detected in the brain tissue by sequencing PCR products, little is known about its in vivo cell tropism and pathogenic potential in the CNS. To detect B19V and investigate the distribution of its target cells in the CNS, we studied brain autopsies of elderly subjects using molecular virology, and optical and electron microscopy methods. Our study detected B19V in brain tissue samples from both encephalopathy and control groups, suggesting virus persistence within the CNS throughout the host’s lifetime. It appears that within the CNS, the main target of B19V is oligodendrocytes. The greatest number of B19V-positive oligodendrocytes was found in the white matter of the frontal lobe. The number was significantly lower in the gray matter of the frontal lobe (p = 0.008) and the gray and white matter of the temporal lobes (p < 0.0001). The morphological changes observed in the encephalopathy group, propose a possible B19V involvement in the demyelination process.

scholarly journals HIV-1 uncoating occurs via a series of rapid biomechanical changes in the core related to individual stages of reverse transcription

2021 ◽  
Author(s):  
Sanela Rankovic ◽  
Akshay Deshpande ◽  
Shimon Harel ◽  
Christopher Aiken ◽  
Itay Rousso
Keyword(s):  
Reverse Transcription ◽  
Viral Genome ◽  
Morphological Changes ◽  
Viral Capsid ◽  
Target Cells ◽  
Viral Core ◽  
Successful Infection ◽  
Capsid Shell ◽  
Hiv 1

AbstractThe HIV core consists of the viral genome and associated proteins encased by a cone-shaped protein shell termed the capsid. Successful infection requires reverse transcription of the viral genome and disassembly of the capsid shell within a cell in a process known as uncoating. The integrity of the viral capsid is critical for reverse transcription, yet the viral capsid must be breached to release the nascent viral DNA prior to integration. We employed atomic force microscopy to study the stiffness changes in HIV-1 cores during reverse transcription in vitro in reactions containing the capsid-stabilizing host metabolite IP6. Cores exhibited a series of stiffness spikes, with up to three spikes typically occurring between 10-30, 40-80, and 120-160 minutes after initiation of reverse transcription. Addition of the reverse transcriptase (RT) inhibitor efavirenz eliminated the appearance of these spikes and the subsequent disassembly of the capsid, thus establishing that both result from reverse transcription. Using timed addition of efavirenz, and analysis of an RNAseH-defective RT mutant, we established that the first stiffness spike requires minus-strand strong stop DNA synthesis, with subsequent spikes requiring later stages of reverse transcription. Additional rapid AFM imaging experiments revealed repeated morphological changes in cores that were temporally correlated with the observed stiffness spikes. Our study reveals discrete mechanical changes in the viral core that are likely related to specific stages of reverse transcription. Our results suggest that reverse-transcription-induced changes in the capsid progressively remodel the viral core to prime it for temporally accurate uncoating in target cells.

scholarly journals Early Events in Kaposi's Sarcoma-Associated Herpesvirus Infection of Target Cells

2009 ◽  
Vol 84 (5) ◽  
pp. 2188-2199 ◽  
Author(s):  
Bala Chandran
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Target Cells ◽  
Mode Of Entry ◽  
Successful Infection ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
Cell Signaling Pathways

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV), the most recently identified member of the herpesvirus family, infects a variety of target cells in vitro and in vivo. This minireview surveys current information on the early events of KSHV infection, including virus-receptor interactions, involved envelope glycoproteins, mode of entry, intracellular trafficking, and initial viral and host gene expression programs. We describe data supporting the hypothesis that KSHV manipulates preexisting host cell signaling pathways to allow successful infection. The various signaling events triggered by infection, and their potential roles in the different stages of infection and disease pathogenesis, are summarized.

scholarly journals In Vitro Response of Immunoregulatory Cytokine Expression in Human Monocytic Cells to Human Parvovirus B19 Capsid

2007 ◽  
Vol 30 (11) ◽  
pp. 2027-2030 ◽  
Author(s):  
Tetsuhiro Fujita ◽  
Hideaki Ikejima ◽  
Nanako Yamagata ◽  
Yuko Kudo ◽  
Keiko Hoshi
Keyword(s):  
Parvovirus B19 ◽  
Cytokine Expression ◽  
Human Parvovirus B19 ◽  
Monocytic Cells ◽  
Immunoregulatory Cytokine ◽  
In Vitro Response

scholarly journals The Genome of Human Parvovirus B19 Can Replicate in Nonpermissive Cells with the Help of Adenovirus Genes and Produces Infectious Virus

2009 ◽  
Vol 83 (18) ◽  
pp. 9541-9553 ◽  
Author(s):  
Wuxiang Guan ◽  
Susan Wong ◽  
Ning Zhi ◽  
Jianming Qiu
Keyword(s):  
Nonstructural Protein ◽  
Parvovirus B19 ◽  
Leukemic Cell ◽  
Progeny Virus ◽  
Human Parvovirus B19 ◽  
Erythroid Progenitor ◽  
Leukemic Cell Lines ◽  
Nonstructural Protein 1 ◽  
293 Cells

ABSTRACT Human parvovirus B19 (B19V) is a member of the genus Erythrovirus in the family Parvoviridae. In vitro, autonomous B19V replication is limited to human erythroid progenitor cells and in a small number of erythropoietin-dependent human megakaryoblastoid and erythroid leukemic cell lines. Here we report that the failure of B19V DNA replication in nonpermissive 293 cells can be overcome by adenovirus infection. More specifically, the replication of B19V DNA in the 293 cells and the production of infectious progeny virus were made possible by the presence of the adenovirus E2a, E4orf6, and VA RNA genes that emerged during the transfection of the pHelper plasmid. Using this replication system, we identified the terminal resolution site and the nonstructural protein 1 (NS1) binding site on the right terminal palindrome of the viral genome, which is composed of a minimal origin of replication spanning 67 nucleotides. Plasmids or DNA fragments containing an NS1 expression cassette and this minimal origin were able to replicate in both pHelper-transfected 293 cells and B19V-semipermissive UT7/Epo-S1 cells. Our results have important implications for our understanding of native B19V infection.

In Vitro Encapsulation of Heterologous dsDNA Into Human Parvovirus B19 Virus-Like Particles

2014 ◽  
Vol 57 (4) ◽  
pp. 309-317 ◽  
Author(s):  
Sandra Paola Sánchez-Rodríguez ◽  
Joana Valeria Enrriquez-Avila ◽  
Juan Miguel Soto-Fajardo ◽  
Carolina Peña-Montes ◽  
Ismael Bustos-Jaimes
Keyword(s):  
Parvovirus B19 ◽  
Human Parvovirus B19 ◽  
Virus Like Particles

scholarly journals The 11-Kilodalton Nonstructural Protein of Human Parvovirus B19 Facilitates Viral DNA Replication by Interacting with Grb2 through Its Proline-Rich Motifs

2018 ◽  
Vol 93 (1) ◽  
Author(s):  
Peng Xu ◽  
Aaron Yun Chen ◽  
Safder S. Ganaie ◽  
Fang Cheng ◽  
Weiran Shen ◽  
...  
Keyword(s):  
Dna Replication ◽  
Nonstructural Protein ◽  
Parvovirus B19 ◽  
Growth Factor Receptor ◽  
Cellular Growth ◽  
Human Parvovirus B19 ◽  
Nonstructural Proteins ◽  
Viral Dna ◽  
Viral Dna Replication

ABSTRACTLytic infection of human parvovirus B19 (B19V) takes place exclusively in human erythroid progenitor cells of bone marrow and fetal liver, which disrupts erythropoiesis. During infection, B19V expresses three nonstructural proteins (NS1, 11-kDa, and 7.5-kDa) and two structural proteins (VP1 and VP2). While NS1 is essential for B19V DNA replication, 11-kDa enhances viral DNA replication significantly. In this study, we confirmed the enhancement role of 11-kDa in viral DNA replication and elucidated the underlying mechanism. We found that 11-kDa specially interacts with cellular growth factor receptor-bound protein 2 (Grb2) during virus infection andin vitro. We determined a high affinity interaction between 11-kDa and Grb2 that has an equilibrium dissociation constant (KD) value of 18.13 nM.In vitro, one proline-rich motif was sufficient for 11-kDa to sustain a strong interaction with Grb2. In consistence,in vivoduring infection, one proline-rich motif was enough for 11-kDa to significantly reduce phosphorylation of extracellular signal-regulated kinase (ERK). Mutations of all three proline-rich motifs of 11-kDa abolished its capability to reduce ERK activity and, accordingly, decreased viral DNA replication. Transduction of a lentiviral vector encoding a short hairpin RNA (shRNA) targetingGrb2decreased the expression of Grb2 as well as the level of ERK phosphorylation, which resulted in an increase of B19V replication. These results, in concert, indicate that the B19V 11-kDa protein interacts with cellular Grb2 to downregulate ERK activity, which upregulates viral DNA replication.IMPORTANCEHuman parvovirus B19 (B19V) infection causes hematological disorders and is the leading cause of nonimmunological fetal hydrops during pregnancy. During infection, B19V expresses two structural proteins, VP1 and VP2, and three nonstructural proteins, NS1, 11-kDa, and 7.5-kDa. While NS1 is essential, 11-kDa plays an enhancing role in viral DNA replication. Here, we elucidated a mechanism underlying 11-kDa protein-regulated B19V DNA replication. 11-kDa is tightly associated with cellular growth factor receptor-bound protein 2 (Grb2) during infection.In vitro, 11-kDa interacts with Grb2 with high affinity through three proline-rich motifs, of which at least one is indispensable for the regulation of viral DNA replication. 11-kDa and Grb2 interaction disrupts extracellular signal-regulated kinase (ERK) signaling, which mediates upregulation of B19V replication. Thus, our study reveals a novel mechanism of how a parvoviral small nonstructural protein regulates viral DNA replication by interacting with a host protein that is predominately expressed in the cytoplasm.

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