scholarly journals Analysis of the Infectious Entry Pathway of Human Papillomavirus Type 33 Pseudovirions

Virology ◽  
2002 ◽  
Vol 299 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Hans-Christoph Selinka ◽  
Tzenan Giroglou ◽  
Martin Sapp
Keyword(s):  
Human Papillomavirus ◽  
Entry Pathway ◽  
Infectious Entry

scholarly journals Recent Advances in Our Understanding of the Infectious Entry Pathway of Human Papillomavirus Type 16

2021 ◽  
Vol 9 (10) ◽  
pp. 2076
Author(s):  
Timothy Keiffer ◽  
Sarah Soorya ◽  
Martin Sapp
Keyword(s):  
Human Papillomavirus ◽  
Entry Pathway ◽  
Human Papillomavirus Type 16 ◽  
Recent Advances ◽  
Infectious Entry

Papillomaviruses are a diverse viral species, but several types such as HPV16 are given special attention due to their contribution towards the pathogenesis of several major cancers. In this review, we will summarize how the knowledge of HPV16 entry has expanded since the last comprehensive HPV16 entry review our lab published in 2017.

scholarly journals Human Papillomavirus Type 31 Uses a Caveolin 1- and Dynamin 2-Mediated Entry Pathway for Infection of Human Keratinocytes

2007 ◽  
Vol 81 (18) ◽  
pp. 9922-9931 ◽  
Author(s):  
Jessica L. Smith ◽  
Samuel K. Campos ◽  
Michelle A. Ozbun
Keyword(s):  
Human Papillomavirus ◽  
Human Keratinocytes ◽  
Dominant Negative ◽  
Half Time ◽  
Caveolin 1 ◽  
Entry Pathway ◽  
Natural Hosts ◽  
Species Specific ◽  
Infectious Entry ◽  
Dynamin 2

ABSTRACT Papillomaviruses are species-specific and epitheliotropic DNA viruses that cause tumors in their natural hosts. Certain infections with genital human papillomavirus (HPV) types are causally related to cervical cancer development. Most papillomaviruses are thought to infect cells via a clathrin-dependent pathway, yet no studies have determined the entry route in permissive host epithelial cells. Employing fluorescently labeled and native virions, we tested the effects of dominant-negative and biochemical inhibitors of cellular endocytosis pathways. Infections of human keratinocytes, a natural host cell type for HPVs, were assessed visually and by infectious entry assays. We found that HPV type 31 (HPV31) entry and initiation of early infection events require both caveolin 1 and dynamin 2 and occur independently of clathrin-mediated endocytosis. Treatment with chlorpromazine and filipin had opposing effects on HPV31 and HPV16 infection. HPV31 entry was remarkably slow, with a half-time of ≈14 h, whereas the entry half-time of HPV16 was 4 h. Consistent with a caveola-mediated entry pathway for HPV31, the virions associated with detergent-resistant lipid rafts. During a 16-h microscopic tracking of HPV31 and HPV16 virions, no colocalization of the two viral types was observed. These data suggest that HPV31 and HPV16 virions use distinct routes for host epithelial cell entry.

scholarly journals Arrangement of L2 within the Papillomavirus Capsid

2008 ◽  
Vol 82 (11) ◽  
pp. 5190-5197 ◽  
Author(s):  
Christopher B. Buck ◽  
Naiqian Cheng ◽  
Cynthia D. Thompson ◽  
Douglas R. Lowy ◽  
Alasdair C. Steven ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Structural Information ◽  
Bimolecular Fluorescence Complementation ◽  
Sexually Transmitted ◽  
Entry Pathway ◽  
Capsid Formation ◽  
Tumor Viruses ◽  
Close Proximity ◽  
Infectious Entry ◽  
L1 And L2

ABSTRACT Papillomaviruses are a family of nonenveloped DNA tumor viruses. Some sexually transmitted human papillomavirus (HPV) types, including HPV type 16 (HPV16), cause cancer of the uterine cervix. Papillomaviruses encode two capsid proteins, L1 and L2. The major capsid protein, L1, can assemble spontaneously into a 72-pentamer icosahedral structure that closely resembles native virions. Although the minor capsid protein, L2, is not required for capsid formation, it is thought to participate in encapsidation of the viral genome and plays a number of essential roles in the viral infectious entry pathway. The abundance of L2 and its arrangement within the virion remain unclear. To address these questions, we developed methods for serial propagation of infectious HPV16 capsids (pseudoviruses) in cultured human cell lines. Biochemical analysis of capsid preparations produced using various methods showed that up to 72 molecules of L2 can be incorporated per capsid. Cryoelectron microscopy and image reconstruction analysis of purified capsids revealed an icosahedrally ordered L2-specific density beneath the axial lumen of each L1 capsomer. The relatively close proximity of these L2 density buttons to one another raised the possibility of homotypic L2 interactions within assembled virions. The concept that the N and C termini of neighboring L2 molecules can be closely apposed within the capsid was supported using bimolecular fluorescence complementation or “split GFP” technology. This structural information should facilitate investigation of L2 function during the assembly and entry phases of the papillomavirus life cycle.

scholarly journals Multiple Heparan Sulfate Binding Site Engagements Are Required for the Infectious Entry of Human Papillomavirus Type 16

2013 ◽  
Vol 87 (21) ◽  
pp. 11426-11437 ◽  
Author(s):  
K. F. Richards ◽  
M. Bienkowska-Haba ◽  
J. Dasgupta ◽  
X. S. Chen ◽  
M. Sapp
Keyword(s):  
Human Papillomavirus ◽  
Heparan Sulfate ◽  
Binding Site ◽  
Human Papillomavirus Type 16 ◽  
Infectious Entry

scholarly journals Topography of the Human Papillomavirus Minor Capsid Protein L2 during Vesicular Trafficking of Infectious Entry

2015 ◽  
Vol 89 (20) ◽  
pp. 10442-10452 ◽  
Author(s):  
Stephen DiGiuseppe ◽  
Timothy R. Keiffer ◽  
Malgorzata Bienkowska-Haba ◽  
Wioleta Luszczek ◽  
Lucile G. M. Guion ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Host Cell ◽  
Capsid Protein ◽  
Conformational Changes ◽  
Transmembrane Protein ◽  
Vesicular Trafficking ◽  
Minor Capsid Protein ◽  
Intracellular Membranes ◽  
Cytosolic Side ◽  
Infectious Entry

ABSTRACTThe human papillomavirus (HPV) capsid is composed of the major capsid protein L1 and the minor capsid protein L2. During entry, the HPV capsid undergoes numerous conformational changes that result in endosomal uptake and subsequent trafficking of the L2 protein in complex with the viral DNA to thetrans-Golgi network. To facilitate this transport, the L2 protein harbors a number of putative motifs that, if capable of direct interaction, would interact with cytosolic host cell factors. These data imply that a portion of L2 becomes cytosolic during infection. Using a low concentration of digitonin to selectively permeabilize the plasma membrane of infected cells, we mapped the topography of the L2 protein during infection. We observed that epitopes within amino acid residues 64 to 81 and 163 to 170 and a C-terminal tag of HPV16 L2 are exposed on the cytosolic side of intracellular membranes, whereas an epitope within residues 20 to 38, which are upstream of a putative transmembrane region, is luminal. Corroborating these findings, we also found that L2 protein is sensitive to trypsin digestion during infection. These data demonstrate that the majority of the L2 protein becomes accessible on the cytosolic side of intracellular membranes in order to interact with cytosolic factors to facilitate vesicular trafficking.IMPORTANCEIn order to complete infectious entry, nonenveloped viruses have to pass cellular membranes. This is often achieved through the viral capsid protein associating with or integrating into intracellular membrane. Here, we determine the topography of HPV L2 protein in the endocytic vesicular compartment, suggesting that L2 becomes a transmembrane protein with a short luminal portion and with the majority facing the cytosolic side for interaction with host cell transport factors.

scholarly journals Infectious Entry Pathway of Adeno-Associated Virus and Adeno-Associated Virus Vectors

2000 ◽  
Vol 74 (6) ◽  
pp. 2777-2785 ◽  
Author(s):  
Jeffrey S. Bartlett ◽  
Rose Wilcher ◽  
R. Jude Samulski
Keyword(s):  
Gene Transfer ◽  
Cell Nucleus ◽  
Specific Cell ◽  
Coated Pits ◽  
Adeno Associated Virus ◽  
Entry Pathway ◽  
Viral Particles ◽  
Hela Cell Lines ◽  
Early Endosomes ◽  
Infectious Entry

ABSTRACT We have investigated the infectious entry pathway of adeno-associated virus (AAV) and recombinant AAV vectors by assessing AAV-mediated gene transfer and by covalently conjugating fluorophores to AAV and monitoring entry by fluorescence microscopy. We examined AAV entry in HeLa cells and in HeLa cell lines which inducibly expressed a dominant interfering mutant of dynamin. The data demonstrate that AAV internalizes rapidly by standard receptor-mediated endocytosis from clathrin-coated pits (half-time <10 min). The lysosomotropic agents ammonium chloride and bafilomycin A1 prevent AAV-mediated gene transfer when present during the first 30 min after the onset of endocytosis, indicating that AAV escapes from early endosomes yet requires an acidic environment for penetration into the cytosol. Following release from the endosome, AAV rapidly moves to the cell nucleus and accumulates perinuclearly beginning within 30 min after the onset of endocytosis. We present data indicating that escape of AAV from the endosome and trafficking of viral particles to the nucleus are unaffected by the presence of adenovirus, the primary helper virus for a productive AAV infection. Within 2 h, viral particles could be detected within the cell nucleus, suggesting that AAV enters the nucleus prior to uncoating. Interestingly, the majority of the intracellular virus particles remain in a stable perinuclear compartment even though gene expression from nuclear AAV genomes can be detected. This suggests that the process of nuclear entry is rate limiting or that AAV entry involves multiple pathways. Nevertheless, these data establish specific points in the AAV infectious entry process and have allowed the generation of a model for future expansion to specific cell types and AAV vector analysis in vivo.

Infectious entry pathway of adenovirus type 2.

1991 ◽  
Vol 65 (11) ◽  
pp. 6061-6070 ◽  
Author(s):  
M J Varga ◽  
C Weibull ◽  
E Everitt
Keyword(s):  
Adenovirus Type ◽  
Entry Pathway ◽  
Infectious Entry ◽  
Adenovirus Type 2

Infectious entry pathway for canine parvovirus

Virology ◽  
1992 ◽  
Vol 186 (2) ◽  
pp. 368-376 ◽  
Author(s):  
Sukla Basak ◽  
Henrietta Turner
Keyword(s):  
Canine Parvovirus ◽  
Entry Pathway ◽  
Infectious Entry

Papillomavirus/cell-interactions initiating the infectious entry pathway

2003 ◽  
Vol 14 (6) ◽  
pp. 259-266 ◽  
Author(s):  
Hans-Christoph Selinka ◽  
Martin Sapp
Keyword(s):  
Cell Interactions ◽  
Entry Pathway ◽  
Infectious Entry

scholarly journals Phosphorylation of Human Papillomavirus Type 16 L2 Contributes to Efficient Virus Infectious Entry

2019 ◽  
Vol 93 (13) ◽  
Author(s):  
Justyna Broniarczyk ◽  
Paola Massimi ◽  
David Pim ◽  
Martina Bergant Marušič ◽  
Michael P. Myers ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Essential Role ◽  
Virus Assembly ◽  
Capsid Proteins ◽  
Viral Capsid ◽  
Acceptor Site ◽  
Hpv 16 ◽  
Viral Genomes ◽  
Infectious Entry ◽  
L1 And L2

ABSTRACTThe human papillomavirus (HPV) capsid comprises two viral proteins, L1 and L2, with the L2 component being essential to ensure efficient endocytic transport of incoming viral genomes. Several studies have previously reported that L1 and L2 are posttranslationally modified, but it is uncertain whether these modifications affect HPV infectious entry. Using a proteomic screen, we identified a highly conserved phospho-acceptor site on the HPV-16 and bovine papillomavirus 1 (BPV-1) L2 proteins. The phospho-modification of L2 and its presence in HPV pseudovirions (PsVs) were confirmed using anti-phospho-L2-specific antibodies. Mutation of the phospho-acceptor sites of both HPV-16 and BPV-1 L2 resulted in the production of infectious virus particles, with no differences in efficiencies of packaging the reporter DNA. However, these mutated PsVs showed marked defects in infectious entry. Further analysis revealed a defect in uncoating, characterized by a delay in the exposure of a conformational epitope on L1 that indicates capsid uncoating. This uncoating defect was accompanied by a delay in the proteolysis of both L1 and L2 in mutated HPV-16 PsVs. Taken together, these studies indicate that phosphorylation of L2 during virus assembly plays an important role in optimal uncoating of virions during infection, suggesting that phosphorylation of the viral capsid proteins contributes to infectious entry.IMPORTANCEThe papillomavirus L2 capsid protein plays an essential role in infectious entry, where it directs the successful trafficking of incoming viral genomes to the nucleus. However, nothing is known about how potential posttranslational modifications may affect different aspects of capsid assembly or infectious entry. In this study, we report the first phospho-specific modification of the BPV-1 and HPV-16 L2 capsid proteins. The phospho-acceptor site is very highly conserved across multiple papillomavirus types, indicating a highly conserved function within the L2 protein and the viral capsid. We show that this modification plays an essential role in infectious entry, where it modulates susceptibility of the incoming virus to capsid disassembly. These studies therefore define a completely new means of regulating the papillomavirus L2 proteins, a regulation that optimizes endocytic processing and subsequent completion of the infectious entry pathway.

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