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 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 Virus-like Particle-Based L2 Vaccines against HPVs: Where Are We Today?

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 18 ◽  
Author(s):  
Rashi Yadav ◽  
Lukai Zhai ◽  
Ebenezer Tumban
Keyword(s):  
Amino Acids ◽  
Capsid Protein ◽  
Hpv Vaccine ◽  
Genital Warts ◽  
Human Papillomaviruses ◽  
Target Antigen ◽  
Sexually Transmitted ◽  
Virus Like Particle ◽  
Protective Antibodies ◽  
Hpv Types

Human papillomaviruses (HPVs) are the most common sexually transmitted infections worldwide. Ninety percent of infected individuals clear the infection within two years; however, in the remaining 10% of infected individuals, the infection(s) persists and ultimately leads to cancers (anogenital cancers and head and neck cancers) and genital warts. Fortunately, three prophylactic vaccines have been approved to protect against HPV infections. The most recent HPV vaccine, Gardasil-9 (a nonavalent vaccine), protects against seven HPV types associated with ~90% of cervical cancer and against two HPV types associated with ~90% genital warts with little cross-protection against non-vaccine HPV types. The current vaccines are based on virus-like particles (VLPs) derived from the major capsid protein, L1. The L1 protein is not conserved among HPV types. The minor capsid protein, L2, on the other hand, is highly conserved among HPV types and has been an alternative target antigen, for over two decades, to develop a broadly protective HPV vaccine. The L2 protein, unlike the L1, cannot form VLPs and as such, it is less immunogenic. This review summarizes current studies aimed at developing HPV L2 vaccines by multivalently displaying L2 peptides on VLPs derived from bacteriophages and eukaryotic viruses. Recent data show that a monovalent HPV L1 VLP as well as bivalent MS2 VLPs displaying HPV L2 peptides (representing amino acids 17–36 and/or consensus amino acids 69–86) elicit robust broadly protective antibodies against diverse HPV types (6/11/16/18/26/31/33/34/35/39/43/44/45/51/52/53/56/58/59/66/68/73) associated with cancers and genital warts. Thus, VLP-based L2 vaccines look promising and may be favorable, in the near future, over current L1-based HPV vaccines and should be explored further.

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 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

scholarly journals In Vitro-Assembled Alphavirus Core-Like Particles Maintain a Structure Similar to That of Nucleocapsid Cores in Mature Virus

2002 ◽  
Vol 76 (21) ◽  
pp. 11128-11132 ◽  
Author(s):  
Suchetana Mukhopadhyay ◽  
Paul R. Chipman ◽  
Eunmee M. Hong ◽  
Richard J. Kuhn ◽  
Michael G. Rossmann
Keyword(s):  
Nucleic Acid ◽  
Capsid Protein ◽  
Structural Information ◽  
Poor Quality ◽  
Icosahedral Symmetry ◽  
Virus Particles ◽  
Surface Lattice ◽  
Infected Cells ◽  
Mature Virus

ABSTRACT In vitro-assembled core-like particles produced from alphavirus capsid protein and nucleic acid were studied by cryoelectron microscopy. These particles were found to have a diameter of 420 Å with 240 copies of the capsid protein arranged in a T=4 icosahedral surface lattice, similar to the nucleocapsid core in mature virions. However, when the particles were subjected to gentle purification procedures, they were damaged, preventing generation of reliable structural information. Similarly, purified nucleocapsid cores isolated from virus-infected cells or from mature virus particles were also of poor quality. This suggested that in the absence of membrane and glycoproteins, nucleocapsid core particles are fragile, lacking accurate icosahedral symmetry.

Accessing Morphosyntax in L1 and L2 Word Recognition

2016 ◽  
Vol 11 (1) ◽  
pp. 26-54 ◽  
Author(s):  
Sina Bosch ◽  
Harald Clahsen
Keyword(s):  
Word Recognition ◽  
Language Processing ◽  
Structural Information ◽  
Masked Priming ◽  
L2 Processing ◽  
Visual Priming ◽  
And Gender ◽  
L1 And L2 ◽  
Case Number ◽  
L2 Word Recognition

In fusional languages, inflectional affixes may encode multiple morphosyntactic features such as case, number, and gender. To determine how these features are accessed during both native (L1) and non-native (L2) word recognition, the present study compares the results from a masked visual priming experiment testing inflected adjectives of German to those of a previous overt (cross-modal) priming experiment on the same phenomenon. While for the L1 group both experiments produced converging results, a group of highly-proficient Russian L2 learners of German showed native-like modulations of repetition priming effects under overt, but not under masked priming conditions. These results indicate that not only affixes but also their morphosyntactic features are accessible during initial form-based lexical access, albeit only for L1 and not for L2 processing. We argue that this contrast is in line with other findings suggesting that non-native language processing is less influenced by structural information than the L1.

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